AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coh...AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography(OCTA),providing a basis for early retinopathy in children with type 1 diabetes.METHODS:This was a retrospective study.A total of 30 patients(3–14y)with type 1 diabetes without clinical diabetic retinopathy(NDR group)were included.A total of 30 age-matched healthy subjects were included as the normal control group(CON group).The HbA1c level in the last 3mo was measured once in the NDR group.The pRNFL thickness and ppVD were automatically measured,and the mean pRNFL and ppVD were calculated in the nasal,inferior,temporal,and superior quadrants.The changes in ppVD and pRNFL in the two groups were analyzed.RESULTS:Compared with CON group,the nasal and superior ppVDs decreased in the NDR group(all P<0.01).The thickness of the nasal pRNFL decreased significantly(P<0.01),while the inferior,temporal and superior pRNFLs slightly decreased but not significant in the NDR group(all P>0.05).Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior(all P<0.01),while inferior and temporal had no significant correlation(all P>0.05).There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant(all P>0.05).There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant(all P>0.05).CONCLUSION:ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring.展开更多
AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulate...AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.展开更多
AIM:To explore the effect of orthokeratology(OK)fitting on retinal vessel density in low to moderate myopia adolescents by using optical coherence tomography angiography.METHODS:Children aged 10 to 14y with a cyclople...AIM:To explore the effect of orthokeratology(OK)fitting on retinal vessel density in low to moderate myopia adolescents by using optical coherence tomography angiography.METHODS:Children aged 10 to 14y with a cycloplegic spherical equivalent refraction of−0.50 diopter(D)to−5.00 D and astigmatism with more than−1.50 D were recruited.The enrolled adolescents were divided into OK group and spectacle group.During regular followup,adolescents were measured respectively at pre-wear,1,3,and 6mo after treatment.The follow-up included uncorrected distance visual acuity(UDVA),axial length(AL),superficial capillary plexus density(SCPD),deep capillary plexus density(DCPD),central retinal thickness(CRT),foveal avascular zone area(FAZ-A),foveal avascular zone perimeter(FAZ-P)and foveal vessel density in a 300-μmwide region around foveal avascular zone(FD-300).The collected data were analyzed using statistical methods.RESULTS:By one month,SCPD significantly increased in the fovea and superior retina,and DCPD significantly increased inferiorly in OK group compared to spectacle group(P<0.05).By three months,there were significant increases in SCPD in the fovea and inferior retina,and DCPD in the parafovea,superior,and inferior retina in OK group(P<0.05),while the increase in SCPD and DCPD in the fovea were observed by six months(P<0.05).The FD-300 significantly increased at every follow-up in OK group compared to spectacle group(P<0.05).No significant differences in the CRT,FAZ-A and FAZ-P and FD-300 were observed between two groups(P>0.05).OK group showed a significant improvement in UDVA after wearing OK,compared to spectacle group(P<0.01),while the AL did not show a significant difference between two groups(P>0.05).CONCLUSION:Short-term OK worn can increase local retinal vessel density in adolescents with low-to-moderate myopia.展开更多
AIM:To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography(OCTA).METHODS:All subjects with chest pain as the main ...AIM:To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography(OCTA).METHODS:All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination.According to the serum lipid levels,the participants were divided into the control group and the dyslipidemia group.The retina thickness and fundus blood flow density were determined using OCTA.RESULTS:The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age-and sexmatched participants without dyslipidemia.The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior(P=0.004 and P=0.014,respectively)and temporal(P=0.015 and P=0.019,respectively)regions,both inner and outer layers.In terms of blood flow density in the macula or optic disk,there was a decreasing trend in the dyslipidemia group compared with the control group,especially in the inferior and temporal regions.CONCLUSION:Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density.Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.展开更多
AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the...AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.展开更多
AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with ...AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with severely obese population(PAT group;24 eyes)and 12 healthy controls(HC group;24 eyes)were recruited.OCTA images were segmented into five[superior(S),nasal(N),inferior(I),temporal(T),and central foveal(C)]or nine[inner superior(IS),outer superior(OS),inner nasal(IN),outer nasal(ON),inner inferior(II),outer inferior(OI),inner temporal(IT),outer temporal(OT),and C]subregions.The superficial vessel density(SVD),retinal thickness(RT),foveal avascular zone(FAZ)parameters,and retinal volume were measured.RESULTS:Visual acuity was significantly different between two groups(0.8±0.17 in PAT group vs 0.2±0.06 in HC group).SVD was significantly lower in PATs in N,T,OS,IN,OT,and ON.The area under the receiver operating characteristic curve(AUC)for T was 0.961[95% confidence interval(CI):0.908 to 1.000],for OS was 0.962(95%CI:0.915 to 1.000).RT was significantly lower in PATs in IS,OS,OI,OT,ON,IT,IN,and II.AUC for OT was 0.935(95%CI:0.870 to 0.999),for IS was 0.915(95%CI:0.838 to 0.992).Angiography results showed significantly lower area and perimeter of FAZ,SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group.CONCLUSION:Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures.These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.展开更多
AIM:To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion(NA-CRAO)via optical coherence tomography angiography(OCTA)and analyze their correlation w...AIM:To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion(NA-CRAO)via optical coherence tomography angiography(OCTA)and analyze their correlation with visual acuity.METHODS:Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into:A type(mild n=29),B type(moderate n=27)and C type(severe n=6)based on the degree of visual loss,retinal edema,and arterial blood flow delay in fundus fluorescence angiography(FFA).Contralateral healthy eyes were used as the control group.Best-corrected visual acuity(BCVA),slit lamp microscopy,indirect ophthalmoscopy,fundus color photography,OCTA,and FFA were performed.Spearman’s correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity.RESULTS:There were no statistically significant differences in age,gender,and intraocular pressure among the three types and the control group(P>0.05).Vessel density in deep capillary plexus(VD-DCP)significantly decreased(P<0.05)in all three types of NA-CRAO patients compared to the control group.Vessel density in superficial vascular plexus(VD-SVP)significantly decreased(P<0.05)in type A patients and choriocapillaris flow area significantly decreased(P<0.05)in type B and type C patients compared to the control group;while outer retinal flow areas significantly increased in the type A(P<0.05)and decreased in type C patients(P<0.05).The retinal thickness significantly increased in type C group(P<0.05).The VD-SVP at fovea in the type A was significantly lower than both of type B and C.The VD-SVP at nasal parafovea in type A and B was significantly lower than type C(P<0.05).The logMAR BCVA of type A was significantly better than that of type B and C groups(P<0.05).Spearman’s correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea(r=0.679,P=0.031)and nasal parafovea(r=0.826,P=0.013).CONCLUSION:OCTA is valuable for assessing retinal ischemia,and evaluating visual impairment.Deep retinal vasculature is commonly affected in all NA-CRAO types.VDSVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.展开更多
AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of...AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.展开更多
BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angioge...BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.展开更多
AIM: To investigate microvascular changes in eyes with central retinal vein occlusion(CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these chang...AIM: To investigate microvascular changes in eyes with central retinal vein occlusion(CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity(BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography(OCTA) automatic measurements of the vessel density in the superficial(SCP) and deep retinal capillary plexus(DCP), the foveal avascular zone(FAZ) area, the FAZ perimeter(PERIM), the vessel density within a 300-μm wide ring surrounding the FAZ(FD-300), the acircularity index(AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age-and sexmatched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were allsignificantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher(all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65(P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness.CONCLUSION: OCTA enables the non-invasive, layerspecific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.展开更多
AIM: To investigate whether 15-Lipoxygenase-1 (15-LOX-1) plays an important role in the regulation of angiogenesis, inhibiting hypoxia-induced proliferation of retinal microvascular endothelial cells (RMVECs) and the ...AIM: To investigate whether 15-Lipoxygenase-1 (15-LOX-1) plays an important role in the regulation of angiogenesis, inhibiting hypoxia-induced proliferation of retinal microvascular endothelial cells (RMVECs) and the underlying mechanism.METHODS: Primary RMVECs were isolated from the retinas of C57/BL6J mice and identified by an evaluation for FITC-marked CD31. The hypoxia models were established with the Bio-bag and evaluated with a blood-gas analyzer. Experiments were performed using RMVECs treated with and without transfer Ad-15-LOX-1 or Ad-vector both under hypoxia and normoxia condition at 12, 24, 48, 72 hours. The efficacy of the gene transfer was assessed by immunofluorescence staining. Cells proliferation was evaluated by the CCK-8 method. RNA and protein expressions of 15-LOX-1, VEGF-A, VEGFR-2, eNOs and PPAR-r were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot.RESULTS: Routine evaluation for FITC-marked CD31 showed that cells were pure. The results of blood-gas analysis showed that when the cultures were exposed to hypoxia for more than 2 hours, the Po2 was 4.5 to 5.4 Kpa. We verified RMVECs could be infected with Ad-15-LOX-1 or Ad-vector via Fluorescence microscopy. CCK-8 analysis revealed that the proliferative capacities of RMVECs in hypoxic group were significantly higher at each time point than they were in normoxic group (P<0.05). In a hypoxic condition, the proliferative capacities of RMVECs in 15-LOX-1 group were significantly inhibited (P<0.05). Real-time RT-PCR analysis revealed that the expressions of VEGF-A, VEGF-R2 and eNOs mRNA increased in hypoxia group compared with normoxia group (P<0.01). However, the expressions of 15-LOX-1, PPAR-r mRNA decreased in hypoxia group compared with normoxia group (P<0.01). It also showed that in a hypoxic condition, the expressions of VEGF-A, VEGF-R2 and eNOs mRNA decreased significantly in 15-LOX-1 group compared with hypoxia group (P<0.01). However, 15-LOX-1 and PPAR-r mRNA increased significantly in 15-LOX-1 group compared with hypoxia group (P<0.01). There was no significant difference of the mRNA expressions between vector group and hypoxia group (P>0.05). Western blot analysis revealed that the expressions of relative proteins were also ranked in that order.CONCLUSION: Our results suggested that 15-LOX-1 and PPAR-r might act as a negative regulator of retinal angiogenesis. And the effect of 15-LOX-1 overexpression is an anti-angiogenic factor in hypoxia-induced retinal neovascularization (RNV). Overexpression 15-LOX-1 on RMVECs of hypoxia-induced RNV blocked signaling cascades by inhibiting hypoxia-induced increases in VEGF family. PPAR-r effect on VEGFR2 could be an additional mechanism whereby 15-LOX-1 inhibited the hypoxia-induced RNV.展开更多
AIM: To investigate biological effects of transthyretin(TTR) on the development of neovascularization under simulated diabetic retinopathy(DR) condition associated with high glucose and hypoxia. METHODS: Human retinal...AIM: To investigate biological effects of transthyretin(TTR) on the development of neovascularization under simulated diabetic retinopathy(DR) condition associated with high glucose and hypoxia. METHODS: Human retinal microvascular endothelial cells(h RECs) were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L;thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 μmol/L Co Cl2. The influence of TTR on h RECs and human retinal pigment epithelial cells(h RPECs) was determined by incubating the cells with 4 μmol/L TTR in normal and abnormal media. A co-culture system was then employed to evaluate the effects of h RPECs on h RECs. RESULTS: Decreased h RECs and h RPECs were observed under abnormal conditions, including high-glucose and hypoxic media. In addition, h RECs were significantly inhibited by 4 μmol/L exogenous TTR during hyperglycemic culture. During co-culture, h RPECs inhibited h RECs in both the normal and abnormal environments.CONCLUSION: h REC growth is inhibited by exogenous TTR under simulated DR environments with high-glucose and hypoxic, particularly in the medium containing 25 mmol/L glucose. h RPECs, which manufacture TTR in the eye, also represses h RECs in the same environment. TTR is predicted to inhibit the proliferation of h RECs and neovascularization.展开更多
AIM: To explore the state of autophagy and related mechanisms in the murine retinal microvascular endothelial cells(RMECs) under hypoxia stimulation.METHODS: The murine RMECs were primarily cultured and randomly divid...AIM: To explore the state of autophagy and related mechanisms in the murine retinal microvascular endothelial cells(RMECs) under hypoxia stimulation.METHODS: The murine RMECs were primarily cultured and randomly divided into three groups: hypoxia group(cultured in 1% O_2 environment), hypoxia+autophagy inhibition group [pretreated with 5 mmol/L 3-methyladenine(3-MA) for 4 h followed by incubation in 1% O_2] and control group(cultured under normoxic condition). The state of autophagy in RMECs was examined by assaying the turnover of light chain 3 B(LC3BB) and expression of Beclin-1, Atg3 and Atg5 proteins with Western blotting, by detecting formation of autophagosomes with transmission electron microscopy(TEM) and by counting the number of GFP+ puncta in RMECs. The protein levels of AMPK, P-AMPK, Akt, P-Akt, m-TOR and P-m TOR were also assayed by Western blotting.RESULTS: Primary murine RMECs were successfully cultured. Under hypoxic conditions, the ratio of LC3BB-Ⅱ/Ⅰ and the expression of Beclin-1, Atg3 and Atg5 proteins were increased when compared with the control group. In addition, the numbers of autophagosome and the GFP+ puncta were also increased under hypoxia. However, pretreatment with 3-MA obviously attenuated these changes in autophagy in RMECs under hypoxia. Protein expression of P-Akt and P-AMPK was increased but P-m TOR level was decreased in cells exposed to hypoxia. CONCLUSION: In murine RMECs autophagy is activated under hypoxia possibly through activation of the AMPK/mTOR signaling pathway.展开更多
AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridiz...AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions,which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2,respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs = 0.211, P= 0.031; rs = 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs = 0.579, P = 0.001; rs = 0.209, P = 0.032),lymph node metastasis (rs = 0.405, P = 0.001; rs= 0.343,P = 0.001) and distant metastasis (rs= 0.474, P = 0.001;rs = 0.468, P = 0.001), but not correlated to tumortype (rs= 0.134, P= 0.173; rs= 0.103, P= 0.145) anddifferentiations (rs = 0.096, P= 0.332; rs = 0.102, P= 0.298).The mean MVD was much higher in the tumors withinfiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t = 5.961, P = 0.001), with non-vessel invasion (t= 7.394, P= 0.001), non-lymph node metastasis (t= 3.819, P= 0.01) and non-distant metastasis (t= 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA(t= 3.207, P= 0.002; t= 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate werelower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bF-GF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.展开更多
·AIM:To perform a quantitative analysis of the peripapillary vessel density(VD)and retinal nerve fiber layer(RNFL)thickness changes in patients with early stage of diabetic retinopathy(DR).·METHODS:In this c...·AIM:To perform a quantitative analysis of the peripapillary vessel density(VD)and retinal nerve fiber layer(RNFL)thickness changes in patients with early stage of diabetic retinopathy(DR).·METHODS:In this case-control study,swept-source optical coherence tomography angiography(SS-OCTA)imaging was used to examine diabetic and age-matched healthy subjects.The optic disc HD 6×6 mm^(2) blood flow imaging scan mode was selected.Automatic software was used to measure the peripapillary VD,capillary vessel density(CVD),and RNLF in an optic nerve head(ONH)filed based on the Garway-Heath map.In addition,the correlation between peripapillary VD,CVD,and RNFL was further investigated.·RESULTS:The cohort consisted of 32 healthy individuals and 72 patients with diabetes(34 eyes with no DR and 38 eyes with mild-moderate NPDR).Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions(P<0.05).Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal(ST)quadrants(P=0.018.P=0.030).In the correlation analysis of each region,the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD(r=0.233,P=0.05;r=0.288.P=0.015).In the TI region,the RNFL thickness was positively correlated with the peripapillary CVD(r=0.237,P=0.047).·CONCLUSION:The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR.The peripapillary VD,CVD and RNFL decrease in early DR,and the RNFL thickness altered in association with the CVD or/and VD in some regions.展开更多
The relationship between the expression of vascular endothelial growth factor(VEGF) and microvascular density(MVD) marked by CD105(CD105-MVD),and that between CD105-MVD and the clinicopathological characteristics of p...The relationship between the expression of vascular endothelial growth factor(VEGF) and microvascular density(MVD) marked by CD105(CD105-MVD),and that between CD105-MVD and the clinicopathological characteristics of primary pterygium were investigated.The streptavidin-biotin complex(SABC) immunohistochemical staining in paraffin-embedded tissues was used to detect the expression of VEGF in 23 cases of primary pterygia and 7 normal conjunctival specimens.The antibody against CD105 was used to display vascular endothelial cells,and MVD was examined by counting the CD105-positive vascular endothelial cells.The correlations of VEGF and CD105-MVD,and those of CD105-MVD and clinicopathological data were analyzed by using SPSS 12.0.The expression of VEGF was significantly increased in epithelia(P=0.000),endothelia and stroma cells(P=0.005) in primary pterygia as compared with normal conjunctivae.The CD105-MVD in pterygia(mean 19.22±6.68) was higher than that in normal conjunctivae(mean 4.00±2.15,P=0.000).MVD in pterygia was significantly associated with the Tan classification(P=0.000) and the VEGF expression level in the stroma(P=0.020),but not with sex(P=0.61),age(P=0.150) or the VEGF expression level in the epithelia(P=0.518).Our results suggest that over-expression of VEGF and high CD105-MVD in primary pterygium may contribute to the progression by increasing angiogenesis and growth of primary pterygium.展开更多
AIM:To evaluate macular microvasculature changes in eyes after pars plana vitrectomy(PPV)and intraocular silicone oil(SO)tamponade for macula-off rhegmatogenous retinal detachment(RRD)using optical coherence tomograph...AIM:To evaluate macular microvasculature changes in eyes after pars plana vitrectomy(PPV)and intraocular silicone oil(SO)tamponade for macula-off rhegmatogenous retinal detachment(RRD)using optical coherence tomography angiography(OCTA).METHODS:Totally 19 eyes(19 patients)with maculaoff RRD who underwent PPV and intraocular SO tamponade were retrospectively reviewed.The parafoveal superficial capillary plexus(SCP)vessel density(VD),deep capillary plexus(DCP)VD,choriocapillaris plexus(CCP)VD,and foveal macular thickness were evaluated using OCTA throughout 16 wk postoperatively.The values of healthy fellow eyes were used as control.RESULTS:The parafoveal SCP,DCP,and CCP VDs were significant increased over time in RRD eyes during the 12 wk postoperatively,then decreased at 16 wk postoperatively(all P<0.01).The ratios of RRD eyes and fellow healthy eyes(r/f ratios)of the SCP and DCP VDs were lower than those of the CCP VD postoperatively(all P<0.05).There were not significant differences in the r/f ratios between SCP and DCP VDs postoperatively(all P>0.05).CONCLUSION:The parafoveal SCP,DCP,and CCP VDs gradually recover over time after PPV surgery with SO tamponade.Long-time SO tamponade might decrease postoperative macular VDs.Compared to parafoveal CCP VD,the parafoveal SCP and DCP VDs were more vulnerable in RRD eyes postoperatively.展开更多
AIM:To observe whether silicone oil(SO)tamponade could decrease macular perfusion after retinal detachment repair.METHODS:A prospective observational case-control study.Patients diagnosed with primary macular off rheg...AIM:To observe whether silicone oil(SO)tamponade could decrease macular perfusion after retinal detachment repair.METHODS:A prospective observational case-control study.Patients diagnosed with primary macular off rhegmatogenous retinal detachment undergoing successful retinal repair surgery with vitrectomy were strictly selected.Optical coherence tomography angiography findings were compared between SO and air tamponade groups.Two postoperative visiting points were set(1 and 3 mo).RESULTS:Totally 29 patients(29 eyes)were enrolled.Twenty cases had SO tamponade while 9 cases were with air tamponade.At the first visiting point,superficial parafoveal vessel density(PFSVD)significantly decreased in the SO group(P=0.0403),especially in the superior quadrant or superior-hemi area(P=0.0089,0.0426,respectively).Parafoveal deep vessel density(PFDVD)had no difference between the two groups.At the second visiting point,all quadrants of PFSVD reduced significantly in the SO group(P=0.0256,0.0001,0.0031,<0.0001 in temporal,superior,nasal,and inferior area,respectively),but PFDVD remained no different.In the air group,all areas of PFSVD showed significantly improving from the first visit to the second one(P=0.0324,0.0001,0.0371,0.0026,in temporal,superior,nasal,and inferior area,respectively);however,almost all quadrants of PFDVD showed no changes during this period.In the SO group,both PFSVD and PFDVD showed no obvious changes between the two visiting points.Besides,parafoveal full retinal thickness in the SO group reduced significantly at both visiting points over the air tamponade,while the foveal avascular zone area showed no difference in the two groups.CONCLUSION:After retinal detachment surgery with vitrectomy and SO tamponade,superficial macular perfusion and full retinal thickness could decrease obviously when compared to air tamponade.This reduction process could persist throughout the tamponade period.展开更多
Objective:To observe the changes of peripapillary vascular density(VD)and its correlation with retinal nerve fiber layer(RNFL)thickness in patients with unilateral retinal vein occlusion(RVO)by optical coherence tomog...Objective:To observe the changes of peripapillary vascular density(VD)and its correlation with retinal nerve fiber layer(RNFL)thickness in patients with unilateral retinal vein occlusion(RVO)by optical coherence tomography angiography(OCTA).Methods:Prospective case-control study.Thirty-two patients(32 eyes)with RVO diagnosed at the Eye Hospital of China Academy of Chinese Medical Sciences from September 2020 to June 2021 were selected.Another 32 outpatients(32 eyes)with normal ocular examination were selected as the normal control group.Optic disc blood flow imaging was performed in all subjects using the OCTA to measure peripapillary RNFL thickness,peripapillary vessel density,optic disc area,and disc rim area.The correlation between peripapillary vascular density and RNFL,optic disc area and disc rim area in eyes with unilateral RVO was analyzed.Results:Compared with the normal control group,the prevalence of hypertension was higher in the unilateral RVO group,and the difference was statistically significant(P<0.05).Compared with the normal control group,the overall,inferior and temporal RNFL thickness around the optic disc was thinner in patients with unilateral RVO,and the difference was statistically significant(P<005).Compared with the normal control group,the overall VD,internal ring,external ring and inferior VD around the optic disc were slightly decreased in patients with unilateral RVO,and the differences were statistically significant(P<0.05).The results of Pearson correlation analysis indicated that RNFL thickness was positively correlated with peripapillary global VD(r=0.648,P<0.001),RNFL thickness was positively correlated with intrapapillary ring VD(r=0.427,P=0.015),and RNFL thickness was positively correlated with peripapillary VD(r=0.666,P<0.001).Conclusion:The results showed that the RNFL thickness around the optic disc was thinner in patients with unilateral RVO,especially in the inferior and temporal area,and the full area VD around the optic disc was decreased,especially in the internal ring,external ring and inferior area.In patients with unilateral RVO,peripapillary RNFL was positively correlated with peripapillary global,internal ring and external ring VD.展开更多
Laser pulse nonlinear transmission measurements through saturable absorbers of known absorption parameters allow the measurement of their energy density. On the other hand, nonlinear transmission measurements of laser...Laser pulse nonlinear transmission measurements through saturable absorbers of known absorption parameters allow the measurement of their energy density. On the other hand, nonlinear transmission measurements of laser pulses of known energy density through absorbing media allow their absorption parameter determination. The peak energy density w0P of second harmonic pulses of a mode-locked titanium sapphire laser at wavelength λP = 400 nm is determined by nonlinear energy transmission measurement TE through the dye ADS084BE (1,4-bis(9-ethyl-3-car-bazovinylene)-2-methoxy-5-(2’-ethyl-hexyloxy)-benzene) in tetrahydrofuran. TE(w0P) calibration curves are calculated for laser pulse peak energy density reading w0P from measured pulse energy transmissions TE. The ground-state absorption cross-section σP and the excited-state absorption cross-section σex at λP, and the number density N0 of the retinal Schiff base isoform RetA in pH 7.4 buffer of the blue-light adapted recombinant rhodopsin fragment of the histidine kinase rhodopsin HKR1 from Chlamydomonas reinhardtii were determined by picosecond titanium sapphire second harmonic laser pulse energy transmission measurement TE through RetA as a function of laser input peak energy density w0P. The complete absorption cross-section spectrum展开更多
基金Supported by Xi’an Municipal Health Commission Scientific Research Project(No.2023yb22)Hospital Level Project of Xi’an Children’s Hospital(No.2021H12No.2022F08).
文摘AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography(OCTA),providing a basis for early retinopathy in children with type 1 diabetes.METHODS:This was a retrospective study.A total of 30 patients(3–14y)with type 1 diabetes without clinical diabetic retinopathy(NDR group)were included.A total of 30 age-matched healthy subjects were included as the normal control group(CON group).The HbA1c level in the last 3mo was measured once in the NDR group.The pRNFL thickness and ppVD were automatically measured,and the mean pRNFL and ppVD were calculated in the nasal,inferior,temporal,and superior quadrants.The changes in ppVD and pRNFL in the two groups were analyzed.RESULTS:Compared with CON group,the nasal and superior ppVDs decreased in the NDR group(all P<0.01).The thickness of the nasal pRNFL decreased significantly(P<0.01),while the inferior,temporal and superior pRNFLs slightly decreased but not significant in the NDR group(all P>0.05).Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior(all P<0.01),while inferior and temporal had no significant correlation(all P>0.05).There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant(all P>0.05).There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant(all P>0.05).CONCLUSION:ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring.
文摘AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.
基金Supported by Medical Research Fund of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Medical Group.
文摘AIM:To explore the effect of orthokeratology(OK)fitting on retinal vessel density in low to moderate myopia adolescents by using optical coherence tomography angiography.METHODS:Children aged 10 to 14y with a cycloplegic spherical equivalent refraction of−0.50 diopter(D)to−5.00 D and astigmatism with more than−1.50 D were recruited.The enrolled adolescents were divided into OK group and spectacle group.During regular followup,adolescents were measured respectively at pre-wear,1,3,and 6mo after treatment.The follow-up included uncorrected distance visual acuity(UDVA),axial length(AL),superficial capillary plexus density(SCPD),deep capillary plexus density(DCPD),central retinal thickness(CRT),foveal avascular zone area(FAZ-A),foveal avascular zone perimeter(FAZ-P)and foveal vessel density in a 300-μmwide region around foveal avascular zone(FD-300).The collected data were analyzed using statistical methods.RESULTS:By one month,SCPD significantly increased in the fovea and superior retina,and DCPD significantly increased inferiorly in OK group compared to spectacle group(P<0.05).By three months,there were significant increases in SCPD in the fovea and inferior retina,and DCPD in the parafovea,superior,and inferior retina in OK group(P<0.05),while the increase in SCPD and DCPD in the fovea were observed by six months(P<0.05).The FD-300 significantly increased at every follow-up in OK group compared to spectacle group(P<0.05).No significant differences in the CRT,FAZ-A and FAZ-P and FD-300 were observed between two groups(P>0.05).OK group showed a significant improvement in UDVA after wearing OK,compared to spectacle group(P<0.01),while the AL did not show a significant difference between two groups(P>0.05).CONCLUSION:Short-term OK worn can increase local retinal vessel density in adolescents with low-to-moderate myopia.
基金Supported by the Science and Technology Commission of Shanghai Municipality(No.20Y11910800)。
文摘AIM:To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography(OCTA).METHODS:All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination.According to the serum lipid levels,the participants were divided into the control group and the dyslipidemia group.The retina thickness and fundus blood flow density were determined using OCTA.RESULTS:The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age-and sexmatched participants without dyslipidemia.The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior(P=0.004 and P=0.014,respectively)and temporal(P=0.015 and P=0.019,respectively)regions,both inner and outer layers.In terms of blood flow density in the macula or optic disk,there was a decreasing trend in the dyslipidemia group compared with the control group,especially in the inferior and temporal regions.CONCLUSION:Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density.Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.
基金Supported by the Shaanxi Province Traditional Chinese Medicine Project(No.SZY-KJCYC-2023-028)。
文摘AIM:To investigate the expression and effect of histone deacetylase 7(HDAC7)in human retinal microvascular endothelial cells(HRMECs)under high glucose condition and related mechanism,and the expression of HDAC7 in the retinal tissue in diabetic rats.METHODS:The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot.LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities.Cell count kit-8(CCK-8),5-ethynyl2’-deoxyuridine(EdU),flow cytometry,scratch test,Transwell test and tube formation assay were used to examine the ability of cell proliferation,migration,and angiogenesis.Finally,a preliminary exploration of its mechanism was performed by Western blot.RESULTS:The expression of HDAC7 was both upregulated in retinal tissues of diabetic rats and high glucosetreated HRMECs.Down-regulation of HDAC7 expression significantly reduced the ability of proliferation,migration,and tube formation,and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.CONCLUSION:High glucose can up-regulate the expression of HDAC7 in HRMECs.Down-regulation of HDAC7 can inhibit HRMECs activities.HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.
基金Supported by National Natural Science Foundation of China(No.82160195)Science and Technology Project of Jiangxi Provincial Department of Education(No.GJJ200169)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2020A0087)Science and Technology Project of Jiangxi Health Commission(No.202130210).
文摘AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with severely obese population(PAT group;24 eyes)and 12 healthy controls(HC group;24 eyes)were recruited.OCTA images were segmented into five[superior(S),nasal(N),inferior(I),temporal(T),and central foveal(C)]or nine[inner superior(IS),outer superior(OS),inner nasal(IN),outer nasal(ON),inner inferior(II),outer inferior(OI),inner temporal(IT),outer temporal(OT),and C]subregions.The superficial vessel density(SVD),retinal thickness(RT),foveal avascular zone(FAZ)parameters,and retinal volume were measured.RESULTS:Visual acuity was significantly different between two groups(0.8±0.17 in PAT group vs 0.2±0.06 in HC group).SVD was significantly lower in PATs in N,T,OS,IN,OT,and ON.The area under the receiver operating characteristic curve(AUC)for T was 0.961[95% confidence interval(CI):0.908 to 1.000],for OS was 0.962(95%CI:0.915 to 1.000).RT was significantly lower in PATs in IS,OS,OI,OT,ON,IT,IN,and II.AUC for OT was 0.935(95%CI:0.870 to 0.999),for IS was 0.915(95%CI:0.838 to 0.992).Angiography results showed significantly lower area and perimeter of FAZ,SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group.CONCLUSION:Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures.These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-016A).
文摘AIM:To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion(NA-CRAO)via optical coherence tomography angiography(OCTA)and analyze their correlation with visual acuity.METHODS:Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into:A type(mild n=29),B type(moderate n=27)and C type(severe n=6)based on the degree of visual loss,retinal edema,and arterial blood flow delay in fundus fluorescence angiography(FFA).Contralateral healthy eyes were used as the control group.Best-corrected visual acuity(BCVA),slit lamp microscopy,indirect ophthalmoscopy,fundus color photography,OCTA,and FFA were performed.Spearman’s correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity.RESULTS:There were no statistically significant differences in age,gender,and intraocular pressure among the three types and the control group(P>0.05).Vessel density in deep capillary plexus(VD-DCP)significantly decreased(P<0.05)in all three types of NA-CRAO patients compared to the control group.Vessel density in superficial vascular plexus(VD-SVP)significantly decreased(P<0.05)in type A patients and choriocapillaris flow area significantly decreased(P<0.05)in type B and type C patients compared to the control group;while outer retinal flow areas significantly increased in the type A(P<0.05)and decreased in type C patients(P<0.05).The retinal thickness significantly increased in type C group(P<0.05).The VD-SVP at fovea in the type A was significantly lower than both of type B and C.The VD-SVP at nasal parafovea in type A and B was significantly lower than type C(P<0.05).The logMAR BCVA of type A was significantly better than that of type B and C groups(P<0.05).Spearman’s correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea(r=0.679,P=0.031)and nasal parafovea(r=0.826,P=0.013).CONCLUSION:OCTA is valuable for assessing retinal ischemia,and evaluating visual impairment.Deep retinal vasculature is commonly affected in all NA-CRAO types.VDSVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.
文摘AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.
基金This study was supported in part by grant from the KeyProject Foundation of Medical Sciences of Jiangsu province(RC2003100)
文摘BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.
基金Supported by National Natural Science Foundation of China(No.81570830)
文摘AIM: To investigate microvascular changes in eyes with central retinal vein occlusion(CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity(BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography(OCTA) automatic measurements of the vessel density in the superficial(SCP) and deep retinal capillary plexus(DCP), the foveal avascular zone(FAZ) area, the FAZ perimeter(PERIM), the vessel density within a 300-μm wide ring surrounding the FAZ(FD-300), the acircularity index(AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age-and sexmatched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were allsignificantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher(all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65(P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness.CONCLUSION: OCTA enables the non-invasive, layerspecific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.
基金National Natural Science Foundation of China (No. 81000393)
文摘AIM: To investigate whether 15-Lipoxygenase-1 (15-LOX-1) plays an important role in the regulation of angiogenesis, inhibiting hypoxia-induced proliferation of retinal microvascular endothelial cells (RMVECs) and the underlying mechanism.METHODS: Primary RMVECs were isolated from the retinas of C57/BL6J mice and identified by an evaluation for FITC-marked CD31. The hypoxia models were established with the Bio-bag and evaluated with a blood-gas analyzer. Experiments were performed using RMVECs treated with and without transfer Ad-15-LOX-1 or Ad-vector both under hypoxia and normoxia condition at 12, 24, 48, 72 hours. The efficacy of the gene transfer was assessed by immunofluorescence staining. Cells proliferation was evaluated by the CCK-8 method. RNA and protein expressions of 15-LOX-1, VEGF-A, VEGFR-2, eNOs and PPAR-r were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot.RESULTS: Routine evaluation for FITC-marked CD31 showed that cells were pure. The results of blood-gas analysis showed that when the cultures were exposed to hypoxia for more than 2 hours, the Po2 was 4.5 to 5.4 Kpa. We verified RMVECs could be infected with Ad-15-LOX-1 or Ad-vector via Fluorescence microscopy. CCK-8 analysis revealed that the proliferative capacities of RMVECs in hypoxic group were significantly higher at each time point than they were in normoxic group (P<0.05). In a hypoxic condition, the proliferative capacities of RMVECs in 15-LOX-1 group were significantly inhibited (P<0.05). Real-time RT-PCR analysis revealed that the expressions of VEGF-A, VEGF-R2 and eNOs mRNA increased in hypoxia group compared with normoxia group (P<0.01). However, the expressions of 15-LOX-1, PPAR-r mRNA decreased in hypoxia group compared with normoxia group (P<0.01). It also showed that in a hypoxic condition, the expressions of VEGF-A, VEGF-R2 and eNOs mRNA decreased significantly in 15-LOX-1 group compared with hypoxia group (P<0.01). However, 15-LOX-1 and PPAR-r mRNA increased significantly in 15-LOX-1 group compared with hypoxia group (P<0.01). There was no significant difference of the mRNA expressions between vector group and hypoxia group (P>0.05). Western blot analysis revealed that the expressions of relative proteins were also ranked in that order.CONCLUSION: Our results suggested that 15-LOX-1 and PPAR-r might act as a negative regulator of retinal angiogenesis. And the effect of 15-LOX-1 overexpression is an anti-angiogenic factor in hypoxia-induced retinal neovascularization (RNV). Overexpression 15-LOX-1 on RMVECs of hypoxia-induced RNV blocked signaling cascades by inhibiting hypoxia-induced increases in VEGF family. PPAR-r effect on VEGFR2 could be an additional mechanism whereby 15-LOX-1 inhibited the hypoxia-induced RNV.
基金Supported by the National Natural Science Foundation of China (No. 81400415)
文摘AIM: To investigate biological effects of transthyretin(TTR) on the development of neovascularization under simulated diabetic retinopathy(DR) condition associated with high glucose and hypoxia. METHODS: Human retinal microvascular endothelial cells(h RECs) were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L;thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 μmol/L Co Cl2. The influence of TTR on h RECs and human retinal pigment epithelial cells(h RPECs) was determined by incubating the cells with 4 μmol/L TTR in normal and abnormal media. A co-culture system was then employed to evaluate the effects of h RPECs on h RECs. RESULTS: Decreased h RECs and h RPECs were observed under abnormal conditions, including high-glucose and hypoxic media. In addition, h RECs were significantly inhibited by 4 μmol/L exogenous TTR during hyperglycemic culture. During co-culture, h RPECs inhibited h RECs in both the normal and abnormal environments.CONCLUSION: h REC growth is inhibited by exogenous TTR under simulated DR environments with high-glucose and hypoxic, particularly in the medium containing 25 mmol/L glucose. h RPECs, which manufacture TTR in the eye, also represses h RECs in the same environment. TTR is predicted to inhibit the proliferation of h RECs and neovascularization.
基金Supported by the National Natural Science Foundation of China(No.81500726)
文摘AIM: To explore the state of autophagy and related mechanisms in the murine retinal microvascular endothelial cells(RMECs) under hypoxia stimulation.METHODS: The murine RMECs were primarily cultured and randomly divided into three groups: hypoxia group(cultured in 1% O_2 environment), hypoxia+autophagy inhibition group [pretreated with 5 mmol/L 3-methyladenine(3-MA) for 4 h followed by incubation in 1% O_2] and control group(cultured under normoxic condition). The state of autophagy in RMECs was examined by assaying the turnover of light chain 3 B(LC3BB) and expression of Beclin-1, Atg3 and Atg5 proteins with Western blotting, by detecting formation of autophagosomes with transmission electron microscopy(TEM) and by counting the number of GFP+ puncta in RMECs. The protein levels of AMPK, P-AMPK, Akt, P-Akt, m-TOR and P-m TOR were also assayed by Western blotting.RESULTS: Primary murine RMECs were successfully cultured. Under hypoxic conditions, the ratio of LC3BB-Ⅱ/Ⅰ and the expression of Beclin-1, Atg3 and Atg5 proteins were increased when compared with the control group. In addition, the numbers of autophagosome and the GFP+ puncta were also increased under hypoxia. However, pretreatment with 3-MA obviously attenuated these changes in autophagy in RMECs under hypoxia. Protein expression of P-Akt and P-AMPK was increased but P-m TOR level was decreased in cells exposed to hypoxia. CONCLUSION: In murine RMECs autophagy is activated under hypoxia possibly through activation of the AMPK/mTOR signaling pathway.
文摘AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions,which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2,respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs = 0.211, P= 0.031; rs = 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs = 0.579, P = 0.001; rs = 0.209, P = 0.032),lymph node metastasis (rs = 0.405, P = 0.001; rs= 0.343,P = 0.001) and distant metastasis (rs= 0.474, P = 0.001;rs = 0.468, P = 0.001), but not correlated to tumortype (rs= 0.134, P= 0.173; rs= 0.103, P= 0.145) anddifferentiations (rs = 0.096, P= 0.332; rs = 0.102, P= 0.298).The mean MVD was much higher in the tumors withinfiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t = 5.961, P = 0.001), with non-vessel invasion (t= 7.394, P= 0.001), non-lymph node metastasis (t= 3.819, P= 0.01) and non-distant metastasis (t= 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA(t= 3.207, P= 0.002; t= 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate werelower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bF-GF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.
基金Supported by College-level Project Fund of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital(No.ynlc201909)。
文摘·AIM:To perform a quantitative analysis of the peripapillary vessel density(VD)and retinal nerve fiber layer(RNFL)thickness changes in patients with early stage of diabetic retinopathy(DR).·METHODS:In this case-control study,swept-source optical coherence tomography angiography(SS-OCTA)imaging was used to examine diabetic and age-matched healthy subjects.The optic disc HD 6×6 mm^(2) blood flow imaging scan mode was selected.Automatic software was used to measure the peripapillary VD,capillary vessel density(CVD),and RNLF in an optic nerve head(ONH)filed based on the Garway-Heath map.In addition,the correlation between peripapillary VD,CVD,and RNFL was further investigated.·RESULTS:The cohort consisted of 32 healthy individuals and 72 patients with diabetes(34 eyes with no DR and 38 eyes with mild-moderate NPDR).Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions(P<0.05).Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal(ST)quadrants(P=0.018.P=0.030).In the correlation analysis of each region,the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD(r=0.233,P=0.05;r=0.288.P=0.015).In the TI region,the RNFL thickness was positively correlated with the peripapillary CVD(r=0.237,P=0.047).·CONCLUSION:The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR.The peripapillary VD,CVD and RNFL decrease in early DR,and the RNFL thickness altered in association with the CVD or/and VD in some regions.
文摘The relationship between the expression of vascular endothelial growth factor(VEGF) and microvascular density(MVD) marked by CD105(CD105-MVD),and that between CD105-MVD and the clinicopathological characteristics of primary pterygium were investigated.The streptavidin-biotin complex(SABC) immunohistochemical staining in paraffin-embedded tissues was used to detect the expression of VEGF in 23 cases of primary pterygia and 7 normal conjunctival specimens.The antibody against CD105 was used to display vascular endothelial cells,and MVD was examined by counting the CD105-positive vascular endothelial cells.The correlations of VEGF and CD105-MVD,and those of CD105-MVD and clinicopathological data were analyzed by using SPSS 12.0.The expression of VEGF was significantly increased in epithelia(P=0.000),endothelia and stroma cells(P=0.005) in primary pterygia as compared with normal conjunctivae.The CD105-MVD in pterygia(mean 19.22±6.68) was higher than that in normal conjunctivae(mean 4.00±2.15,P=0.000).MVD in pterygia was significantly associated with the Tan classification(P=0.000) and the VEGF expression level in the stroma(P=0.020),but not with sex(P=0.61),age(P=0.150) or the VEGF expression level in the epithelia(P=0.518).Our results suggest that over-expression of VEGF and high CD105-MVD in primary pterygium may contribute to the progression by increasing angiogenesis and growth of primary pterygium.
文摘AIM:To evaluate macular microvasculature changes in eyes after pars plana vitrectomy(PPV)and intraocular silicone oil(SO)tamponade for macula-off rhegmatogenous retinal detachment(RRD)using optical coherence tomography angiography(OCTA).METHODS:Totally 19 eyes(19 patients)with maculaoff RRD who underwent PPV and intraocular SO tamponade were retrospectively reviewed.The parafoveal superficial capillary plexus(SCP)vessel density(VD),deep capillary plexus(DCP)VD,choriocapillaris plexus(CCP)VD,and foveal macular thickness were evaluated using OCTA throughout 16 wk postoperatively.The values of healthy fellow eyes were used as control.RESULTS:The parafoveal SCP,DCP,and CCP VDs were significant increased over time in RRD eyes during the 12 wk postoperatively,then decreased at 16 wk postoperatively(all P<0.01).The ratios of RRD eyes and fellow healthy eyes(r/f ratios)of the SCP and DCP VDs were lower than those of the CCP VD postoperatively(all P<0.05).There were not significant differences in the r/f ratios between SCP and DCP VDs postoperatively(all P>0.05).CONCLUSION:The parafoveal SCP,DCP,and CCP VDs gradually recover over time after PPV surgery with SO tamponade.Long-time SO tamponade might decrease postoperative macular VDs.Compared to parafoveal CCP VD,the parafoveal SCP and DCP VDs were more vulnerable in RRD eyes postoperatively.
基金Wenzhou Municipal Science and Technology Bureau(No.Y20180730)。
文摘AIM:To observe whether silicone oil(SO)tamponade could decrease macular perfusion after retinal detachment repair.METHODS:A prospective observational case-control study.Patients diagnosed with primary macular off rhegmatogenous retinal detachment undergoing successful retinal repair surgery with vitrectomy were strictly selected.Optical coherence tomography angiography findings were compared between SO and air tamponade groups.Two postoperative visiting points were set(1 and 3 mo).RESULTS:Totally 29 patients(29 eyes)were enrolled.Twenty cases had SO tamponade while 9 cases were with air tamponade.At the first visiting point,superficial parafoveal vessel density(PFSVD)significantly decreased in the SO group(P=0.0403),especially in the superior quadrant or superior-hemi area(P=0.0089,0.0426,respectively).Parafoveal deep vessel density(PFDVD)had no difference between the two groups.At the second visiting point,all quadrants of PFSVD reduced significantly in the SO group(P=0.0256,0.0001,0.0031,<0.0001 in temporal,superior,nasal,and inferior area,respectively),but PFDVD remained no different.In the air group,all areas of PFSVD showed significantly improving from the first visit to the second one(P=0.0324,0.0001,0.0371,0.0026,in temporal,superior,nasal,and inferior area,respectively);however,almost all quadrants of PFDVD showed no changes during this period.In the SO group,both PFSVD and PFDVD showed no obvious changes between the two visiting points.Besides,parafoveal full retinal thickness in the SO group reduced significantly at both visiting points over the air tamponade,while the foveal avascular zone area showed no difference in the two groups.CONCLUSION:After retinal detachment surgery with vitrectomy and SO tamponade,superficial macular perfusion and full retinal thickness could decrease obviously when compared to air tamponade.This reduction process could persist throughout the tamponade period.
文摘Objective:To observe the changes of peripapillary vascular density(VD)and its correlation with retinal nerve fiber layer(RNFL)thickness in patients with unilateral retinal vein occlusion(RVO)by optical coherence tomography angiography(OCTA).Methods:Prospective case-control study.Thirty-two patients(32 eyes)with RVO diagnosed at the Eye Hospital of China Academy of Chinese Medical Sciences from September 2020 to June 2021 were selected.Another 32 outpatients(32 eyes)with normal ocular examination were selected as the normal control group.Optic disc blood flow imaging was performed in all subjects using the OCTA to measure peripapillary RNFL thickness,peripapillary vessel density,optic disc area,and disc rim area.The correlation between peripapillary vascular density and RNFL,optic disc area and disc rim area in eyes with unilateral RVO was analyzed.Results:Compared with the normal control group,the prevalence of hypertension was higher in the unilateral RVO group,and the difference was statistically significant(P<0.05).Compared with the normal control group,the overall,inferior and temporal RNFL thickness around the optic disc was thinner in patients with unilateral RVO,and the difference was statistically significant(P<005).Compared with the normal control group,the overall VD,internal ring,external ring and inferior VD around the optic disc were slightly decreased in patients with unilateral RVO,and the differences were statistically significant(P<0.05).The results of Pearson correlation analysis indicated that RNFL thickness was positively correlated with peripapillary global VD(r=0.648,P<0.001),RNFL thickness was positively correlated with intrapapillary ring VD(r=0.427,P=0.015),and RNFL thickness was positively correlated with peripapillary VD(r=0.666,P<0.001).Conclusion:The results showed that the RNFL thickness around the optic disc was thinner in patients with unilateral RVO,especially in the inferior and temporal area,and the full area VD around the optic disc was decreased,especially in the internal ring,external ring and inferior area.In patients with unilateral RVO,peripapillary RNFL was positively correlated with peripapillary global,internal ring and external ring VD.
文摘Laser pulse nonlinear transmission measurements through saturable absorbers of known absorption parameters allow the measurement of their energy density. On the other hand, nonlinear transmission measurements of laser pulses of known energy density through absorbing media allow their absorption parameter determination. The peak energy density w0P of second harmonic pulses of a mode-locked titanium sapphire laser at wavelength λP = 400 nm is determined by nonlinear energy transmission measurement TE through the dye ADS084BE (1,4-bis(9-ethyl-3-car-bazovinylene)-2-methoxy-5-(2’-ethyl-hexyloxy)-benzene) in tetrahydrofuran. TE(w0P) calibration curves are calculated for laser pulse peak energy density reading w0P from measured pulse energy transmissions TE. The ground-state absorption cross-section σP and the excited-state absorption cross-section σex at λP, and the number density N0 of the retinal Schiff base isoform RetA in pH 7.4 buffer of the blue-light adapted recombinant rhodopsin fragment of the histidine kinase rhodopsin HKR1 from Chlamydomonas reinhardtii were determined by picosecond titanium sapphire second harmonic laser pulse energy transmission measurement TE through RetA as a function of laser input peak energy density w0P. The complete absorption cross-section spectrum
