AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult my...AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram.METHODS:It’s a prospective cohort study.Patients with anisometropic myopia of refractive difference≥2.0 diopters(D)who underwent SMILE between September 2020 and March 2021 were enrolled.Clinical features and visual function were assessed preoperatively and at 1wk,1,3,and 6mo after the operation.The examination included tests for uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),refractive errors,effectiveness index(preoperative CDVA/postoperative UDVA),safety index(postoperative CDVA/preoperative CDVA),nomogram and stereoscopic function.Paired t-test,Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables,and Pearson Chi-squared test was used for categorical variables.RESULTS:The study involved 45 consecutive patients(average age:25.0±6.9y;82 out of 90 eyes underwent SMILE,while 8 eyes were not operated).The average preoperative spherical equivalent(SE)was-4.74±0.22 D.Six months after surgery,the effectiveness index was 1.05±0.12,and the safety index was 1.09±0.11.Seventy eyes(85.4%)exhibited SE correction error within±0.5 D.The percentage of eyes with Titmus stereoscopic function equal to or less than 200”significantly increased from 55.6%preoperatively to 88.9%postoperatively(P<0.05).There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio.CONCLUSION:SMILE is safe,effective and predictable in correcting myopic anisometropia,and it improves stereoscopic visual function of anisometropia patients.The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.展开更多
AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudativ...AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.展开更多
·AIM: To examine the expression of high mobility group box-1(HMGB-1) and intercellular adhesion molecule-1(ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two m...·AIM: To examine the expression of high mobility group box-1(HMGB-1) and intercellular adhesion molecule-1(ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier(BRB) and blood-brain barrier(BBB) in a rat model of type 2 diabetes.·METHODS: The type-2 diabetes mellitus(DM) model was established with a high-fat and high-glucose diet combined with streptozotocin(STZ). Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay(ELISA).·RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection(P <0.01). The serum levels of fasting insulin,Insulin resistance homeostatic model assessment(IRHOMA),total cholesterol(TC), total triglycerides(TG) and low density lipoprotein cholesterol(LDL-C) in the DM rats significantly higher than those in the controls(all P <0.01).HMGB-1(0.96±0.03, P <0.01) and ICAM-1(0.76±0.12, P <0.05) levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1(0.83±0.13, P <0.01) and ICAM-1(1.15 ±0.08, P <0.01) levels in the hippocampal tissues in the DM rats were alsosignificantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls(P <0.01).However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats.·CONCLUSION: BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.展开更多
● AIM: To compare of lens oxidative damage induced by vitrectomy and/or hyperoxia in rabbit.● METHODS: Sixteen New Zealand rabbits(2.4-2.5 kg) were randomly divided into two groups(Group A, n=12; Group B, n=4). In G...● AIM: To compare of lens oxidative damage induced by vitrectomy and/or hyperoxia in rabbit.● METHODS: Sixteen New Zealand rabbits(2.4-2.5 kg) were randomly divided into two groups(Group A, n=12; Group B, n=4). In Group A, the right eyes were treated with vitrectomy and systemic hyperoxia(oxygen concentration: 80%-85%, 1 ATA, 4h/d)(Group A-right), and the left eyes were treated with hyperoxia without vitrectomy surgery(Group A-left). Four rabbits in group B(eight eyes) were untreated as the controls. Lens transparency was monitored with a slit lamp and recorded before and after vitrectomy. After hyperoxic treatment for 6mo, the eyeballs were removed and the lens cortices(containing the capsules) and nuclei were separated for further morphological and biochemical evaluation.● RESULTS: Six months after treatments, there were no significant morphological changes in the lenses in any experimental group when observed with a slit lamp. However, the levels of water-soluble proteins and ascorbate, and the activities of catalase and Na^+-K^+-ATPase were significantlyreduced, whereas the levels of malondialdehyde and transforming growth factor β2(TGF-β2) were significantly elevated, in both the cortices and nuclei of eyes treated with vitrectomy and hyperoxia. The increase in proteinglutathione mixed disulfides and the reduction in watersoluble proteins were more obvious in the lens nuclei. The levels of ascorbate in the vitreous fluid were also reduced after vitrectomy, whereas TGF-β2 increased after vitrectomy and hyperoxia. Systemic hyperoxia exposure increased these effects.● CONCLUSION: Removal of the intact vitreous gel with vitrectomy and exposing the lens to increased oxygen from the retina induce lens oxidation and aggregation. Thus, an intact vitreous gel structure may protect the lens from oxidative insult and maintain lens transparency.展开更多
AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was i...AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.展开更多
AIM: To investigate the characteristics of uveitis in a secondary hospital in southern China.METHODS: We reviewed all records of patients with uveitis at Hengli Hospital from January 2008 to December2011. Demographic ...AIM: To investigate the characteristics of uveitis in a secondary hospital in southern China.METHODS: We reviewed all records of patients with uveitis at Hengli Hospital from January 2008 to December2011. Demographic data, past history, ophthalmic examinations and other laboratory tests were analyzed.RESULTS: One hundred and ninety-nine uveitis patients were enrolled in this study, including 134(67.3%) males and 65 females(32.7%) with an average age of 41.0 ±15.1y. The anatomical distribution included103(51.8%) cases of anterior uveitis, followed by panuveitis(65, 32.7%), posterior uveitis(29, 14.6%) and intermediate uveitis(2, 1.0%). Of the 98(49.2%) non-idiopathic cases, there were 10.1% Behcet's disease,9.5% Vogt-Koyanagi-Harada(VKH) syndrome, 7.5%infectious uveitis, 7.5% traumatic uveitis and 3.5%postoperative uveitis.CONCLUSION: Idiopathic anterior and posterior uveitis,Behcet's disease, VKH syndrome, infectious uveitis and traumatic uveitis are the most common uveitis entities in a secondary hospital in southern China. Additional measures should be taken to prevent infectious and traumatic uveitis.展开更多
AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPD...AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain reaction.RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs.CONCLUSION: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.展开更多
AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One ...AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One hundred healthy individuals served as controls. Peripheral blood was obtained from VKH patients and healthy controls. Th lymphocyte subsets were analyzed by flow cytometry. Plasma concentration of interleukin(IL)-17, IL-10, transforming growth factor(TGF)-β, IL-23 and IL-6 was examined by enzyme-linked immunosorbent assay(ELISA). RESULTS: VKH patients with active uveitis had significantly higher percentages of both Th1 and Th17 cells and lower percentages of regulatory T(Treg) cells as compared with inactive VKH patients and healthy controls. Th1/Th2 and Th17/Treg ratios were also significantly elevated in active VKH patients. The percentages of Th1, Th17 and Treg cells and the Th1/Th2, Th17/Treg ratio did not differ between inactive VKH patients and healthy controls. There was no difference concerning the percentage of Th2 cells among all the groups. VKH patients with active uveitis showed an elevated level of peripheral Th17 related cytokines levels(TGF-β, IL-6, IL-23, and IL-17) and a decreased level of Treg related cytokines(IL-10) compared with inactive VKH patients and healthy controls. Inactive VKH patients showed no differences in peripheral Th17 related cytokines(TGF-β, IL-6, IL-23, and IL-17) and Treg related cytokines(IL-10) levels compared with healthy controls. CONCLUSION: Th1 and Th17 cells are significantly increased and Treg cells significantly decreased in active VKH compared with inactive VKH or healthy controls. Therefore, Th lymphocyte subset analysis may serve as a disease biomarker for VKH.展开更多
AIM:To examine the association between the single nucleotide polymorphisms (SNPs)of matrix metalloprotease-9 (MMP-9) gene and primary angleclosure glaucoma(PACG)in a Chinese Han population.METHODS:DNA samples were ext...AIM:To examine the association between the single nucleotide polymorphisms (SNPs)of matrix metalloprotease-9 (MMP-9) gene and primary angleclosure glaucoma(PACG)in a Chinese Han population.METHODS:DNA samples were extracted from peripheral-blood mononuclear cells of 214 PACG patients and 224 healthy controls.Genotyping of rs3918249,rs3918254,rs17577 and rs3787268 in MMP-9was performed using polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)analysis and the direct sequencing technique.The association between these genetic polymorphisms and risk of PACG was estimated by χ2 test.RESULTS:The distributions of rs3918249,rs3918254,rs17577 and rs3787268 genotypes among cases and healthy controls were compatible with that from HardyWeinberg equilibrium(HWE,P>0.05).The increased frequency of CC and CT genotypes of rs3918254 were observed in PACG patients compared to healthy controls[P=0.006,P corrected(Pcorr)=0.048].The haplotype analysis showed that the CCGG haplotype was nominal associated with PACG(P=0.015),however,the significant was lost when the Bonferroni correction was used(Pcorr=0.105).CONCLUSION:Our results revealed that rs3918254 in MMP-9 may be a susceptible locus to PACG in China,people with the CC and CT genotypes of rs3918254 are more susceptible to PACG.The susceptibility to PACG inChinese Han patients may be not influenced by SNPs rs3918249,rs3787268 and rs17577 in MMP-9.展开更多
AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the ca...AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the candidate gene region(rs11792633,rs7025417,rs10975519 and rs1048274 in IL33;rs2310220,rs12712142,rs13424006 and rs3821204 in IL1RL1)were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array i PLEX platform.RESULTS:A statistically significant association was observed between IL1RL1 rs12712142 and BD patients.The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls(OR=0.8,95%CI:0.69-0.94,Pc=0.039);the genotype distribution(Pc=0.043)and additive and dominant genetic model analyses(OR=0.8,95%CI:0.69-0.94,Pc=0.040 and OR=0.72,95%CI:0.58-0.88,Pc=0.011)also indicated a strong association between rs12712142 and BD patients.CONCLUSION:This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population,indicating a protective role of IL1RL1 in the pathogenesis of BD.展开更多
Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing stud...Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.展开更多
Behcet’s disease is defined as a multisystemic inflammatory disease.Although the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a p...Behcet’s disease is defined as a multisystemic inflammatory disease.Although the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a profound influence on the development of Behcet’s disease.To explore the genetic factors for Behcet’s disease,our group investigated the association of Behcet’s disease with multiple immune response genes and has identified multiple Behcet’s disease-related immunoregulatory pathways in the Chinese Han population.A large number of gene polymorphisms were studied including STAT4,IL23R,CD40,CCR1/CCR3,STAT3,OPN,IL17,JAK2,MCP-1,CTLA4,PD-1,PD-L1,PD-L2,TGRBR3,CCR6,PTPN22,FCRL3,IRF5,SUMO4 and UBAC2.Significant associations were found between Behcet’s disease and STAT4,IL23R,CD40,CCR1/CCR3,STAT3,MCP-1,TGFBR3,FCRL3,SUMO4,UBAC2.These genetic predisposition studies support an important role for both lymphocyte differentiation as well as ubiquitination pathways.These findings are helpful in elucidating the pathogenesis of Behcet’s disease and hopefully will allow the development of novel treatment regimes.展开更多
Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclea...Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.展开更多
基金Supported by the National Natural Science Foundation of China(No.81970832No.81870650)+2 种基金the Key Project of the Chongqing Health Commission(No.2018MSXM003No.2018GDRC008)Natural Science Foundation of Chongqing Science and Technology Bureau(No.cstc2021jcyj-msxmX0967).
文摘AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram.METHODS:It’s a prospective cohort study.Patients with anisometropic myopia of refractive difference≥2.0 diopters(D)who underwent SMILE between September 2020 and March 2021 were enrolled.Clinical features and visual function were assessed preoperatively and at 1wk,1,3,and 6mo after the operation.The examination included tests for uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),refractive errors,effectiveness index(preoperative CDVA/postoperative UDVA),safety index(postoperative CDVA/preoperative CDVA),nomogram and stereoscopic function.Paired t-test,Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables,and Pearson Chi-squared test was used for categorical variables.RESULTS:The study involved 45 consecutive patients(average age:25.0±6.9y;82 out of 90 eyes underwent SMILE,while 8 eyes were not operated).The average preoperative spherical equivalent(SE)was-4.74±0.22 D.Six months after surgery,the effectiveness index was 1.05±0.12,and the safety index was 1.09±0.11.Seventy eyes(85.4%)exhibited SE correction error within±0.5 D.The percentage of eyes with Titmus stereoscopic function equal to or less than 200”significantly increased from 55.6%preoperatively to 88.9%postoperatively(P<0.05).There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio.CONCLUSION:SMILE is safe,effective and predictable in correcting myopic anisometropia,and it improves stereoscopic visual function of anisometropia patients.The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.
基金Supported by the National Natural Science Foundation of China(No.81670881)
文摘AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.
基金Supported by the Project of Education Bureau Foundation of Hubei Province(No.Q20151901)
文摘·AIM: To examine the expression of high mobility group box-1(HMGB-1) and intercellular adhesion molecule-1(ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier(BRB) and blood-brain barrier(BBB) in a rat model of type 2 diabetes.·METHODS: The type-2 diabetes mellitus(DM) model was established with a high-fat and high-glucose diet combined with streptozotocin(STZ). Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay(ELISA).·RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection(P <0.01). The serum levels of fasting insulin,Insulin resistance homeostatic model assessment(IRHOMA),total cholesterol(TC), total triglycerides(TG) and low density lipoprotein cholesterol(LDL-C) in the DM rats significantly higher than those in the controls(all P <0.01).HMGB-1(0.96±0.03, P <0.01) and ICAM-1(0.76±0.12, P <0.05) levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1(0.83±0.13, P <0.01) and ICAM-1(1.15 ±0.08, P <0.01) levels in the hippocampal tissues in the DM rats were alsosignificantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls(P <0.01).However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats.·CONCLUSION: BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.
基金Supported by National Natural Science Foundation of China(No.30872837)
文摘● AIM: To compare of lens oxidative damage induced by vitrectomy and/or hyperoxia in rabbit.● METHODS: Sixteen New Zealand rabbits(2.4-2.5 kg) were randomly divided into two groups(Group A, n=12; Group B, n=4). In Group A, the right eyes were treated with vitrectomy and systemic hyperoxia(oxygen concentration: 80%-85%, 1 ATA, 4h/d)(Group A-right), and the left eyes were treated with hyperoxia without vitrectomy surgery(Group A-left). Four rabbits in group B(eight eyes) were untreated as the controls. Lens transparency was monitored with a slit lamp and recorded before and after vitrectomy. After hyperoxic treatment for 6mo, the eyeballs were removed and the lens cortices(containing the capsules) and nuclei were separated for further morphological and biochemical evaluation.● RESULTS: Six months after treatments, there were no significant morphological changes in the lenses in any experimental group when observed with a slit lamp. However, the levels of water-soluble proteins and ascorbate, and the activities of catalase and Na^+-K^+-ATPase were significantlyreduced, whereas the levels of malondialdehyde and transforming growth factor β2(TGF-β2) were significantly elevated, in both the cortices and nuclei of eyes treated with vitrectomy and hyperoxia. The increase in proteinglutathione mixed disulfides and the reduction in watersoluble proteins were more obvious in the lens nuclei. The levels of ascorbate in the vitreous fluid were also reduced after vitrectomy, whereas TGF-β2 increased after vitrectomy and hyperoxia. Systemic hyperoxia exposure increased these effects.● CONCLUSION: Removal of the intact vitreous gel with vitrectomy and exposing the lens to increased oxygen from the retina induce lens oxidation and aggregation. Thus, an intact vitreous gel structure may protect the lens from oxidative insult and maintain lens transparency.
基金Supported partially by National Natural Science Foundation of China(No.81271033,81470621)
文摘AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.
基金Supported by National Natural Science Foundation of China(No.81470620)Natural Science Foundation Project of Chongqing(No.cstc2013jcyjA 10015)+1 种基金Dongguan Municipal Science and Technology Projects from the Bureau of Science and Technology of Dongguan City(No.20101051500102)Medical Science Fundation Project of Guangdong Health Department(No.A2011719)
文摘AIM: To investigate the characteristics of uveitis in a secondary hospital in southern China.METHODS: We reviewed all records of patients with uveitis at Hengli Hospital from January 2008 to December2011. Demographic data, past history, ophthalmic examinations and other laboratory tests were analyzed.RESULTS: One hundred and ninety-nine uveitis patients were enrolled in this study, including 134(67.3%) males and 65 females(32.7%) with an average age of 41.0 ±15.1y. The anatomical distribution included103(51.8%) cases of anterior uveitis, followed by panuveitis(65, 32.7%), posterior uveitis(29, 14.6%) and intermediate uveitis(2, 1.0%). Of the 98(49.2%) non-idiopathic cases, there were 10.1% Behcet's disease,9.5% Vogt-Koyanagi-Harada(VKH) syndrome, 7.5%infectious uveitis, 7.5% traumatic uveitis and 3.5%postoperative uveitis.CONCLUSION: Idiopathic anterior and posterior uveitis,Behcet's disease, VKH syndrome, infectious uveitis and traumatic uveitis are the most common uveitis entities in a secondary hospital in southern China. Additional measures should be taken to prevent infectious and traumatic uveitis.
基金Supported by the National Natural Science Foundation of China (No.81870643)
文摘AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) patients.METHODS: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain reaction.RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs.CONCLUSION: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.
基金Supported by National Natural Science Foundation of China(No.30772013)Basic Research Program of Chongqing(No.cstc2015jcyjA10112)
文摘AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One hundred healthy individuals served as controls. Peripheral blood was obtained from VKH patients and healthy controls. Th lymphocyte subsets were analyzed by flow cytometry. Plasma concentration of interleukin(IL)-17, IL-10, transforming growth factor(TGF)-β, IL-23 and IL-6 was examined by enzyme-linked immunosorbent assay(ELISA). RESULTS: VKH patients with active uveitis had significantly higher percentages of both Th1 and Th17 cells and lower percentages of regulatory T(Treg) cells as compared with inactive VKH patients and healthy controls. Th1/Th2 and Th17/Treg ratios were also significantly elevated in active VKH patients. The percentages of Th1, Th17 and Treg cells and the Th1/Th2, Th17/Treg ratio did not differ between inactive VKH patients and healthy controls. There was no difference concerning the percentage of Th2 cells among all the groups. VKH patients with active uveitis showed an elevated level of peripheral Th17 related cytokines levels(TGF-β, IL-6, IL-23, and IL-17) and a decreased level of Treg related cytokines(IL-10) compared with inactive VKH patients and healthy controls. Inactive VKH patients showed no differences in peripheral Th17 related cytokines(TGF-β, IL-6, IL-23, and IL-17) and Treg related cytokines(IL-10) levels compared with healthy controls. CONCLUSION: Th1 and Th17 cells are significantly increased and Treg cells significantly decreased in active VKH compared with inactive VKH or healthy controls. Therefore, Th lymphocyte subset analysis may serve as a disease biomarker for VKH.
基金Supported by National Natural Science Foundation of China(No.81270990No.81070723)
文摘AIM:To examine the association between the single nucleotide polymorphisms (SNPs)of matrix metalloprotease-9 (MMP-9) gene and primary angleclosure glaucoma(PACG)in a Chinese Han population.METHODS:DNA samples were extracted from peripheral-blood mononuclear cells of 214 PACG patients and 224 healthy controls.Genotyping of rs3918249,rs3918254,rs17577 and rs3787268 in MMP-9was performed using polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)analysis and the direct sequencing technique.The association between these genetic polymorphisms and risk of PACG was estimated by χ2 test.RESULTS:The distributions of rs3918249,rs3918254,rs17577 and rs3787268 genotypes among cases and healthy controls were compatible with that from HardyWeinberg equilibrium(HWE,P>0.05).The increased frequency of CC and CT genotypes of rs3918254 were observed in PACG patients compared to healthy controls[P=0.006,P corrected(Pcorr)=0.048].The haplotype analysis showed that the CCGG haplotype was nominal associated with PACG(P=0.015),however,the significant was lost when the Bonferroni correction was used(Pcorr=0.105).CONCLUSION:Our results revealed that rs3918254 in MMP-9 may be a susceptible locus to PACG in China,people with the CC and CT genotypes of rs3918254 are more susceptible to PACG.The susceptibility to PACG inChinese Han patients may be not influenced by SNPs rs3918249,rs3787268 and rs17577 in MMP-9.
基金the National Natural Science Foundation of China (No.81770917)。
文摘AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the candidate gene region(rs11792633,rs7025417,rs10975519 and rs1048274 in IL33;rs2310220,rs12712142,rs13424006 and rs3821204 in IL1RL1)were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array i PLEX platform.RESULTS:A statistically significant association was observed between IL1RL1 rs12712142 and BD patients.The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls(OR=0.8,95%CI:0.69-0.94,Pc=0.039);the genotype distribution(Pc=0.043)and additive and dominant genetic model analyses(OR=0.8,95%CI:0.69-0.94,Pc=0.040 and OR=0.72,95%CI:0.58-0.88,Pc=0.011)also indicated a strong association between rs12712142 and BD patients.CONCLUSION:This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population,indicating a protective role of IL1RL1 in the pathogenesis of BD.
基金We thank the families for participation in this study,and we thank Novogene Technology Co.,Ltd.,for the WES sequencing and analysis.This work was supported by the National Natural Science Foundation Project of China(82070951,82271078)the National Natural Science Foundation Key Program(81930023)+3 种基金The Innovative Research Group Project of Chongqing Education Commission(CXQT19015)the Innovation Supporting Plan of Overseas Study of Chongqing(cx2018010)the National Key Clinical Specialties Construction Program of China,the Chongqing Branch of the National Clinical Research Center for Ocular Diseases,the Chongqing Key Laboratory of Ophthalmology(CSTC,2008CA5003)the Program for Youth Innovation in Future Medicine,Chongqing Medical University(w0047).
文摘Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.
文摘Behcet’s disease is defined as a multisystemic inflammatory disease.Although the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a profound influence on the development of Behcet’s disease.To explore the genetic factors for Behcet’s disease,our group investigated the association of Behcet’s disease with multiple immune response genes and has identified multiple Behcet’s disease-related immunoregulatory pathways in the Chinese Han population.A large number of gene polymorphisms were studied including STAT4,IL23R,CD40,CCR1/CCR3,STAT3,OPN,IL17,JAK2,MCP-1,CTLA4,PD-1,PD-L1,PD-L2,TGRBR3,CCR6,PTPN22,FCRL3,IRF5,SUMO4 and UBAC2.Significant associations were found between Behcet’s disease and STAT4,IL23R,CD40,CCR1/CCR3,STAT3,MCP-1,TGFBR3,FCRL3,SUMO4,UBAC2.These genetic predisposition studies support an important role for both lymphocyte differentiation as well as ubiquitination pathways.These findings are helpful in elucidating the pathogenesis of Behcet’s disease and hopefully will allow the development of novel treatment regimes.
基金supported by the National Natural Science Foundation Project of China(No.82070951,82271078 and 81873678)the Innovative Research Group Project of Chongqing Education Commission(China)(No.CXQT19015)+5 种基金the Natural Science Foundation Project of Chongqing,China(No.cstc2019jcyjmsxmx0120)the Innovation Supporting Plan of Overseas Study of Chongqing,China(No.cx2018010)the Chongqing Education Commission(China)(No.KJQN202000406)the National Key Clinical Specialties Construction Program of China,Chongqing Branch of National Clinical Research Center for Ocular Diseasesthe Chongqing Key Laboratory of Ophthalmology(China)(CSTC,No.2008CA5003)Natural Science Foundation Project of Chongqing Medical University(China)(No.W0047).
文摘Uveitis,a vision-threatening inflammatory disease worldwide,is closely related to resident microglia.Retinal microglia are the main immune effector cells with strong plasticity,but their role in uveitis remains unclear.N6-methyladenosine(m^(6)A)modification has been proven to be involved in the immune response.Therefore,we in this work aimed to identify the potentially crucial m^(6)A regulators of microglia in uveitis.Through the single-cell sequencing(scRNA-seq)analysis and experimental verification,we found a significant decrease in the expression of fat mass and obesity-associated protein(FTO)in retinal microglia of uveitis mice and human microglia clone 3(HMC3)cells with inflammation.Additionally,FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia.Mechanistically,the RNA-seq data and rescue experiments showed that glypican 4(GPC4)was the target of FTO,which regulated microglial inflammation mediated by the TLR4/NF-κB pathway.Moreover,RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m^(6)A“reader”YTH domain family protein 3(YTHDF3).Finally,the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis(EAU)inflammation by promoting the GPC4/TLR4/NF-κB signaling axis,and this could be attenuated by the TLR4 inhibitor TAK-242.Collectively,a decreased FTO could facilitate microglial inflammation in EAU,suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis.
