AIM: To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats.METHODS: The streptozotocin(STZ)-induced diabetic rats were randomly divided into 6 gro...AIM: To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats.METHODS: The streptozotocin(STZ)-induced diabetic rats were randomly divided into 6 groups: diabetes mellitus(DM) group(saline, 3 μL/eye); RC28-E at low(0.33 μg/μL, 3 μL), medium(1 μg/μL, 3 μL), and high(3 μg/μL,3 μL) dose groups; vascular endothelial growth factor(VEGF) Trap group(1 μg/μL, 3 μL); fibroblast growth factor(FGF) Trap group(1 μg/μL, 3 μL). Normal control group was included. At week 1 and 4 following diabetic induction,the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining.Glial fibrillary acidic protein(GFAP) expression was examined by immunofluorescence. Blood-retinal barrier(BRB) breakdown was assessed by Evans blue assay.Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy(TEM).Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay(ELISA). The retinal expression of intercellular cell adhesion molecule-1(ICAM-1), tumor necrosis factor-α(TNF-α), VEGF and FGF genes was examined by quantitative polymerase chain reaction(qPCR).RESULTS: TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap(all P<0.05), the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap(P<0.01). GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent.Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina(P<0.01). TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs.CONCLUSION: Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment,in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy(DR).展开更多
AIM:To investigate the influence of unilateral congenital ptosis on the development of the eye and vision in children.METHODS:In this prospective observational study,41 patients with unilateral congenital ptosis were ...AIM:To investigate the influence of unilateral congenital ptosis on the development of the eye and vision in children.METHODS:In this prospective observational study,41 patients with unilateral congenital ptosis were enrolled(age range 3-15y).The blepharoptosis was divided into 3 subgroups according to the margin reflex distance-1(MRD-1),including mild group(MRD-1>2 mm),moderate group(0<MRD-1<2 mm),and severe group(MRD-1<0 mm).The fellow eyes served as controls.All subjects underwent ocular examinations,including axial length,keratometry,and refractive error.RESULTS:The incidence of astigmatism(ptotic eyes:58.5%vs fellow eyes:24.4%,P=0.002)and magnitude of cylindrical power(ptotic eyes:-0.86±0.79 D vs fellow eyes:-0.43±0.63 D,P=0.003)differed significantly between the ptotic eyes and the fellow eyes.The spherical equivalent refraction(P=0.006),spherical power(P=0.01),cylindrical power(P=0.011),axial length-corneal radius(AL/CR)ratio(P=0.009),frequency of hyperopia(P=0.002)and astigmatism(P=0.004)were significantly different among the ptotic eye subgroups and the fellow eye group.In addition,in patients with congenital ptosis,the incidence of amblyopia is 43.9%and the incidence of anisometropia is 24.4%.More importantly,the ratio of AL/CR showed significantly positive correlation with the severity of ptosis(P=0.002).CONCLUSION:Congenital ptosis may lead to a delayed eyeball development in the aspect of AL/CR.The risk of amblyopia is also increased due to visual deprivation and aggravated anisometropia,particularly in severe ptosis case.展开更多
Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo tr...Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).展开更多
AIM:To investigate the effect of electroacupuncture(EA)on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lensinduced myopia(LIM).METHODS:Guinea pigs were rand...AIM:To investigate the effect of electroacupuncture(EA)on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lensinduced myopia(LIM).METHODS:Guinea pigs were randomly divided into normal control(NC)group,LIM group,LIM+SHAM acupoint(LIM+SHAM)group,and LIM+EA group.Animals in the NC group received no intervention,while those in other three groups were covered with-6.0 diopter(D)lenses on right eyes.Meanwhile,animals in the LIM+EA group received EA at Hegu(LI4)combined with Taiyang(EX-HN5)acupoints,while those in the LIM+SHAM group were treated at sham points.After treatments for 1,2,and 4wk,morphological changes in ciliary muscles were observed with hematoxylin and eosin(H&E)staining and nick end labeling(TUNEL),and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction(qPCR)and Western blot.Additionally,the adenosine triphosphate(ATP)contents were also determined in ciliary muscles.RESULTS:Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group.The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups,whereas those in the LIM+EA group improved significantly.TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups,whereas reduced in the LIM+EA group.ATP contents showed a significant decrease in the LIM and LIM+SHAM groups,whereas increased after EA treatment.Compared with the NC group,the dynamin-related protein 1(DRP1),Caspase3,and apoptotic protease activator 1(APAF1)levels were significantly increased in the LIM group and decreased in the LIM+EA group.CONCLUSION:The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.展开更多
AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional o...AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P <0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P <0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.展开更多
文摘AIM: To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats.METHODS: The streptozotocin(STZ)-induced diabetic rats were randomly divided into 6 groups: diabetes mellitus(DM) group(saline, 3 μL/eye); RC28-E at low(0.33 μg/μL, 3 μL), medium(1 μg/μL, 3 μL), and high(3 μg/μL,3 μL) dose groups; vascular endothelial growth factor(VEGF) Trap group(1 μg/μL, 3 μL); fibroblast growth factor(FGF) Trap group(1 μg/μL, 3 μL). Normal control group was included. At week 1 and 4 following diabetic induction,the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining.Glial fibrillary acidic protein(GFAP) expression was examined by immunofluorescence. Blood-retinal barrier(BRB) breakdown was assessed by Evans blue assay.Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy(TEM).Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay(ELISA). The retinal expression of intercellular cell adhesion molecule-1(ICAM-1), tumor necrosis factor-α(TNF-α), VEGF and FGF genes was examined by quantitative polymerase chain reaction(qPCR).RESULTS: TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap(all P<0.05), the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap(P<0.01). GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent.Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina(P<0.01). TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs.CONCLUSION: Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment,in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy(DR).
基金Supported by the Project of Science and Technology of Tianjin(No.17ZXHLSY00030).
文摘AIM:To investigate the influence of unilateral congenital ptosis on the development of the eye and vision in children.METHODS:In this prospective observational study,41 patients with unilateral congenital ptosis were enrolled(age range 3-15y).The blepharoptosis was divided into 3 subgroups according to the margin reflex distance-1(MRD-1),including mild group(MRD-1>2 mm),moderate group(0<MRD-1<2 mm),and severe group(MRD-1<0 mm).The fellow eyes served as controls.All subjects underwent ocular examinations,including axial length,keratometry,and refractive error.RESULTS:The incidence of astigmatism(ptotic eyes:58.5%vs fellow eyes:24.4%,P=0.002)and magnitude of cylindrical power(ptotic eyes:-0.86±0.79 D vs fellow eyes:-0.43±0.63 D,P=0.003)differed significantly between the ptotic eyes and the fellow eyes.The spherical equivalent refraction(P=0.006),spherical power(P=0.01),cylindrical power(P=0.011),axial length-corneal radius(AL/CR)ratio(P=0.009),frequency of hyperopia(P=0.002)and astigmatism(P=0.004)were significantly different among the ptotic eye subgroups and the fellow eye group.In addition,in patients with congenital ptosis,the incidence of amblyopia is 43.9%and the incidence of anisometropia is 24.4%.More importantly,the ratio of AL/CR showed significantly positive correlation with the severity of ptosis(P=0.002).CONCLUSION:Congenital ptosis may lead to a delayed eyeball development in the aspect of AL/CR.The risk of amblyopia is also increased due to visual deprivation and aggravated anisometropia,particularly in severe ptosis case.
基金Supported by LUO Yuankai Research Fund for Young Scholars(No.20190810)National Natural Science Foundation of China(No.82174429)。
文摘Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).
基金Supported by National Key R&D Program of China(No.2021YFC2702103,No.2021YFC2702100)the National Natural Science Foundation of China(No.82104937)the Key R&D Program of Shandong Province(No.2019GSF108252).
文摘AIM:To investigate the effect of electroacupuncture(EA)on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lensinduced myopia(LIM).METHODS:Guinea pigs were randomly divided into normal control(NC)group,LIM group,LIM+SHAM acupoint(LIM+SHAM)group,and LIM+EA group.Animals in the NC group received no intervention,while those in other three groups were covered with-6.0 diopter(D)lenses on right eyes.Meanwhile,animals in the LIM+EA group received EA at Hegu(LI4)combined with Taiyang(EX-HN5)acupoints,while those in the LIM+SHAM group were treated at sham points.After treatments for 1,2,and 4wk,morphological changes in ciliary muscles were observed with hematoxylin and eosin(H&E)staining and nick end labeling(TUNEL),and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction(qPCR)and Western blot.Additionally,the adenosine triphosphate(ATP)contents were also determined in ciliary muscles.RESULTS:Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group.The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups,whereas those in the LIM+EA group improved significantly.TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups,whereas reduced in the LIM+EA group.ATP contents showed a significant decrease in the LIM and LIM+SHAM groups,whereas increased after EA treatment.Compared with the NC group,the dynamin-related protein 1(DRP1),Caspase3,and apoptotic protease activator 1(APAF1)levels were significantly increased in the LIM group and decreased in the LIM+EA group.CONCLUSION:The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.
基金Supported by Shanxi China Scientific and Technological Project(No.2007031096-1)Ph.D.Program Foundation of Ministry of Education of China(No.20111202110008)
文摘AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P <0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P <0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.
