Oxidative Stress Participates in Age-Related Cataract Formation by Disrupting Connection between Lens Epithelial Cells through c-Src/VEGF Pathway.

PURPOSE: To observe the effects of oxidative stress on vascular endothelial growth factor (VEGF) and connections of lens epithelial cells. METHODS: Human lens epithelium of patients with age-related cataract (ARC), both SRA01/04 cells and whole mice lens stimulated by H2O2 were employed. VEGF in human aqueous humor of ARC-patients and the supernatant of SRA01/04 cells was determined by ELISA. The expressions of VEFG in human lens epithelium were detected by immunofluorescence staining. Multiple linear regression analysis and spearman rank-order correlation were used to determine the associations between VEGF and parameters of ARC individuals. In H2O2-induced SRA01/04 cells, Catalase (CAT), PP1 (inhibitor of c-Src kinase) and Avastin (VEGF antibody) were used to inhibit the effects of H2O2, activation of c-Src kinase and VEGF, which were detected by Western blot. The alterations of ZO-1 and N-cadherin were tested by immunofluorescence staining and Western blot. In H2O2-induced whole lens, the changes of opacification area in different treatment of inhibitors were observed. RESULTS: The secretion of VEGF in aqueous humor and expression of VEGF in the lens epithelium of ARC patients increased significantly with age. In H2O2-induced SRA01/04 cells, the VEGF in the supernatant was increased with the culture duration and the dose of H2O2. The expressions of p-Src418 and VEGF were also up-regulated, whereas the expressions of ZO-1 and N-cadherin were down-regulated. CAT effectively prevented these changes induced by H2O2, while PP1 inhibited not only p-Src418 but also up-regulation of VEGF, Avastin partially inhibited VEGF up-regulation. Both PP1 and Avastin prevented down-regulation of ZO-1 and N-cadherin, respectively, but Avastin combined with PP1 had no significant synergistic effects. In H2O2-induced cataract, CAT prevented development of opacification area effectively, and PP1 and Avastin did partially. CONCLUSIONS: Oxidative stress disrupts connections of lens epithelial cells by activating c-Src/VEGF, inhibiting which may prevent cataract.

Long-term efficacy and safety of YAG laser vitreolysis for vision degrading myodesopsia.

AIM: To assess the long-term efficacy and safety of yttrium-aluminum garnet (YAG) laser vitreolysis for vision degrading myodesopsia (VDM) caused by posterior vitreous detachment (PVD). METHODS: This retrospective study reviewed VDM patients of PVD type undergoing YAG laser vitreolysis. The baseline demographic information, the patterns of floaters, the number of floaters, and the subjective improvement of floater sympotoms (ranging from 0 to 100%) from medical records were collected. Significant improvement was defined as a relief of floater symptoms of ≥50% at the final visit. The long-term efficacy and safety of YAG laser vitreolysis were analyzed. The risk factors linked to significant improvement of floater symptoms were defined using univariate and multivariate logistic regression analyses. RESULTS: The final analysis included 221 patients with VDM. The mean age of patients was 61.08±7.74y, and the mean length of follow-up was 21.38±5.61mo. Totally 57.01% of patients experienced a significant improvement in their floater symptoms after YAG laser therapy, and none of them developed delayed retinal abnormalities such as retinal tears or detachments. Age (OR=1.049, 95%CI=1.007-1.092, P=0.021) was identified as a significant risk factor for significant improvement in VDM. CONCLUSION: YAG laser vitreolysis is an effective and secure treatment for PVD-type VDM, and patients of advanced age are more likely to get favorable outcomes.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion.

AIM: To assess the long-term outcomes of treating macular edema (ME) associated with central retinal vein occlusion (CRVO) with a regimen of "5+pro re nata (PRN)". METHODS: This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO (non-iCRVO group, n=15) and ischemic CRVO (iCRVO group, n=12). The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab, followed by reinjections as needed or PRN. Retinal laser photocoagulation or intravitreal dexamethasone implants (DEX) were implemented in both groups when necessary. The best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were recorded at baseline, at 1, 2, 3, 4, 5, 6, and 12mo, and at the final visit. The efficacy rates of BCVA and CRT before and after treatment were calculated. The number of injections at each visit and the incidence of adverse events were also recorded. RESULTS: The patients, aged 59.4±15.1y, were followed up for 24.7±8.8mo (range: 15-42mo). After treatment, BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR (P=0.038) at the final visit in all patients. Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points, but there was no statistical significance (P=0.197 and 0.33, respectively). The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups (all P<0.001). The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection, 48.15% for BCVA and 62.96% for CRT after 5 consecutive injections, and 74.08% for BCVA and 100% for CRT at the end of follow up. The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups (P>0.05). Laser treatment was applied to all eyes in the iCRVO group, while only 5 patients in the non-iCRVO group. Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch. DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group. CONCLUSION: The 5+PRN anti-vascular endothelial growth factor (VEGF) regimen is found to be safe and effective for both iCRVO and non-iCRVO, especially in the iCRVO group. The best regimen for such patients needs to be further investigated. Adjuvant laser therapy and DEX are necessary in some cases.

Efficacy and safety of atropine at different concentrations in prevention of myopia progression in Asian children: a systematic review and Meta-analysis of randomized clinical trials.

AIM: To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children. METHODS: Databases (PubMed, EMBASE, the Cochrane Library and Web of science) were comprehensively searched from inception to April 2022. Types of studies included were randomized clinical trials (RCTs). The published languages were limited to English. Two researchers assessed the quality of included studies independently using Cochrane risk of bias tool based on the Cochrane Handbook for Systematic Reviews of Interventions. Funnel plots and Egger's test were used for detection of publication bias. Meta-analyses were conducted using STATA (version 15.0; StataCorp). RESULTS: A total of 15 RCTs involving 2268 patients were included in the study. In the atropine group, spherical equivalent progressed at a significantly lower rate [weighted mean difference (WMD)=0.39, 95% confidence interval (CI): 0.23, 0.54] than in the control group. A WMD of 0.15 mm was associated with less axial elongation (95%CI -0.19, -0.10). Different doses showed statistically significant differences (P<0.05) and an improved effect could result from a higher concentration. Changes in photopic pupil size and mesopic pupil size in atropine group is 0.70 mm (95%CI: 0.33, 1.06) and 0.38 mm (95%CI: 0.22, 0.54) more than the control group. In the present Meta-analysis, no changes in accommodative amplitude (AA) were associated with atropine administration. Atropine administration increased the risk of adverse effects by 1.37 times. CONCLUSION: Concentrations of less than 1% atropine are able to effectively retard diopter and axis growth of myopia in Asian children in a dose-dependent manner. Meanwhile, it caused pupil enlargement, but induced no change in the AA within this range. Further study is required to determine the dosage needed to achieve maximum efficacy and minimal side effects.

Agreement of intraocular pressure measurement with Corvis ST, non-contact tonometer, and Goldmann applanation tonometer in children with ocular hypertension and related factors.

AIM: To access the agreement of intraocular pressure (IOP) values obtained from biomechanically corrected tonometer [Corvis ST (CST)], non-contact tonometer (NCT), and Goldmann applanation tonometer (GAT) in children with NCT measured-IOP (NCT-IOP) values of 22 mm Hg or more, and related factors. METHODS: A total of 51 eyes with NCT-IOP≥22 mm Hg in children aged 7 to 14y were examined and IOP was measured by CST, NCT, and GAT. Based on GAT measured IOP (GAT-IOP), ocular hypertension (OHT) group (≥22 mm Hg, 24 eyes) and the non-OHT group (<22 mm Hg, 27 eyes) were defined. We compared the agreement of the three measurements, i.e., CST measured IOP (CST-IOP), GAT-IOP, and NCT-IOP, and further analyzed the correlation between the differences in tonometry readings, central corneal thickness (CCT), axial length (AL), optic disc rim volume, and age. RESULTS: Compared with the OHT group, thicker CCT, larger rim volume, and higher differences between NCT-IOP and GAT-IOP, were found in the non-OHT group. The differences between CST-IOP and GAT-IOP were lower than the differences between NCT-IOP and GAT-IOP in both groups. The mean differences in CST-IOP and GAT-IOP were 1.26 mm Hg (95% limit of agreement ranged from 0.1 to 2.41 mm Hg, OHT group) and 1.20 mm Hg (95% limit of agreement ranged from -0.5 to 3.00 mm Hg, non-OHT group), and the mean differences in NCT and GAT were 3.90 mm Hg (95% limit of agreement ranged from -0.19 to 9.70 mm Hg, OHT group) and 6.00 mm Hg (95% limit of agreement ranged from 1.50 to 10.50 mm Hg, non-OHT group). The differences between CST-IOP and GAT-IOP were not related to CCT, age, and AL in both groups; while the differences between NCT-IOP and GAT-IOP were related to CCT in the OHT group (r=0.93, P<0.001) and to CCT and AL in the non-OHT group (r=0.66, P<0.001, r=-0.81, P<0.001). CONCLUSION: The accuracy of NCT in the diagnosis of pediatric OHT is low. The agreement of CST-IOP and GAT-IOP was significantly higher in children with and without OHT than in those with NCT-IOP and GAT-IOP. Therefore, CST can be used as a good alternative for IOP measurement in children. The impacts of CCT and AL on NCT measurement need to be fully considered when managing childhood IOP.

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion.

AIM: To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy (DR) or retinal vein occlusion (RVO). METHODS: This is a retrospective case control study. The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor (VEGF) for patients diagnosed with macular edema secondary to DR (DME) or RVO (RVO-ME) at Xijing Hospital from August 2021 to July 2022. Meanwhile, aqueous humor samples during vitrectomy from patients with idiopathic macular hole (IMH) were also collected and served as controls. The aqueous humor concentrations of VEGF, platelet-derived factor (PDGF), interleukin (IL)-6, IL-8, IL-18, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) were measured with Human Premixed Multi-Analyte Kit (Luminex). The difference of the aqueous cytokines and the correlation between the two diseases were analyzed. RESULTS: A total of 40 eyes of 38 patients were enrolled in the study, including 13 eyes of 11 DME patients (DME group), 16 eyes of 16 RVO-ME patients (RVO-ME group) and 11 eyes of 11 IMH patients (control group). The VEGF, PDGF, IL-6, IL-8, and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group (all P<0.05), the levels of TNF-α was higher in the DME group than in the control group (P<0.05). The VEGF, IL-6, MCP-1, and TNF-α levels in the aqueous humor were significantly higher in the DR group than those in the RVO group (all P<0.05). Correlation analyses revealed that there were complex positive correlations between IL-6, IL-8, IL-18, MCP-1, and TNF-α levels in the aqueous humor of eyes with two diseases. CONCLUSION: Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME, the roles of these factors are more significant or more likely to be activated in DR patients, suggesting different treatment strategies should be considered for the two diseases.

Effects of bevacizumab on the neovascular membrane of proliferative diabetic retinopathy: reduction of endothelial cells and expressions of VEGF and HIF-1α.

PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have recently been used intravitreally during the perioperative period for proliferative diabetic retinopathy (PDR). However, the mechanism of theraputic effects of the agents remains unclear. This study aimed to investigate the effects of intravitreal bevacizumab (IVB) on retinal vascular endothelial cells and expressions of VEGF and hypoxia inducible factor-1α (HIF-1α) in PDR. METHODS: Twenty-four patients with PDR were enrolled and randomized to two groups. Twelve eyes of 12 patients of each group received either an intravitreal injection of 1.25 mg bevacizumab or a sham injection 6 days before vitrectomy. Neovascular membranes (NVMs) were collected during pars plana vitrectomy. The numbers of vascular endothelial cells in the NVMs were counted after staining with hematoxylin and eosin and von Willebrand. The expressions of VEGF and HIF-1α in the NVMs were detected through immunohistochemistry. Ten epiretinal membrane specimens from patients with proliferative vitreoretinopathy (PVR) without IVB treatment were set as an additional control. RESULTS: The number of vascular endothelial cells in NVMs of the IVB pretreated group was significantly lower than that of the sham group (21.5±3.94 versus 41.33±7.44, p=0.003). The IVB pretreated group also showed significantly lower levels of VEGF and HIF-1α in NVMs than those of the sham group (P(HIF-1α)=0.02, P(VEGF)<0.001). A stepwise regression analysis showed that IVB was a significant negative predictor for the numbers of vascular endothelial cells (ß=-0.89, p<0.001) and the expressions of VEGF (ß=-0.85, p<0.001) and HIF-1α (ß=-0.64, p=0.001) in PDR patients. Epiretinal membranes of the PVR group showed negative staining of VEGF and HIF-1α. CONCLUSIONS: Pretreatment with IVB in patients with PDR significantly decreased vascular endothelial cells and expressions of VEGF and HIF-1α, which further supports preoperative use of IVB in such patients.

[Innovation and application are vital for translational research in ophthalmology].

Although the resource devoted for scientific research increased substantially in recent years, the quality of our basic and clinical study still leaves much to be improved. Besides the shortcomings in administration of research funding, our researchers, as the entity of scientific work, should fully recognize that innovation and application are vital for basic and clinical research in ophthalmology. It is emphasized that the principles and methods in an innovative study, including comprehensive grasp for up-to-date information, proposal of a key project, collaboration of multi-disciplines, through design of a study, and acceleration of application in practice, should be followed in order to make new advances in our cause in ophthalmology.

[The problems that should be noticed in choosing animal models with diabetic retinopathy].

Animal models of diabetes mellitus (DM) are vital for research on pathogenesis and pharmaceutical therapy of diabetic retinopathy (DR). At present, diabetic animal models include chemicals or dietary-induced models, transgenic or gene knockout mice, and spontaneous mice, etc. Among these models, rat model induced by streptozotocin is simple and imminent with high repeatability, which made it the most popular one. However, no available diabetic model could reproduce all vascular and neural pathological changes observed in human non-proliferative and proliferative DR. It is also known that not all DM models could lead to DR. In addition, features and severity of retinopathy in the model depend on animal kinds, animal lifespan, time course of the disease and induction methods. Therefore, researchers should consider characteristics and limitations of different models while choosing suitable DM model based on research objectives and resources. It is particularly emphasized that the results from animal models do not always fit human conditions.

[Regulatory effects of ninjurin-1 on adhesion of myeloid cells in the retina at the early stage of diabetic rats].

OBJECTIVE: To investigate the regulatory effects of ninjurin-1 on adhesion of myeloid cells in the retina at the early stage of diabetic rats. METHODS: Experimental study. The rat diabetic model was induced by intraperitoneal injection of streptozotocin. After 2 months of diabetes induction, 27 diabetic rats were randomly chosen and assigned to 3 groups, including diabetes and phosphate buffered saline (PBS) injection group (group B), diabetes and anti-Ninj-1 injection group (group C) and diabetes and anti-IgG injection group (group D), with 9 rats in each group. Nine age matched health rats were chosen as control group (group A). Retinal leukostasis was quantified with acridine orange leukocyte fluorography. Retinal myeloid cell infiltration activity was measured by enzyme linked immunosorbent assay of myeloperoxidase (MPO). The differences of the mean values among the four groups were analyzed by one-factor analysis of variance. The multiple comparisons of the mean values among the four groups were analyzed by LSD-t analysis. RESULTS: According to the results of the acridine orange leukocyte fluorography, the numbers of leukocyte adhesion in the four groups were 49.66 ± 13.51, 153.66 ± 20.43, 85.33 ± 15.03 and 156.33 ± 11.53, respectively. The differences among them were significant (F = 143.34, P = 0.000). The numbers of leukocyte adhesion in the group C were significantly lower than that in group B (P = 0.000, 95%CI: -82.68 - -53.98). The levels of retinal MPO in the four groups were (15.66 ± 2.08), (27.66 ± 2.51), (18.02 ± 2.01) and (26.66 ± 3.21) µg/L, respectively. The differences among them were significant (F = 17.61, P = 0.010). The level of retinal MPO in the group C was significantly lower than that in group B (P = 0.010, 95%CI: -14.37 - -4.95). CONCLUSIONS: Ninj-1 may play a role in the mediation of the adhesion of myeloid cell to the rat retina of early-stage of diabetes in vivo.

Intraocular lens removal or not during vitrectomy for acute infectious endophthalmitis after cataract surgery.

At present, the incidence of infectious endophthalmitis after cataract surgery has been significantly reduced, but it is still a serious complication. Removal or not of the intraocular lens (IOL) during vitrectomy in cases with a moderate or severe inflammation is controversial. In order to call upon more discussion, we publish the article entitled "Timely vitrectomy without intraocular lens removal for acute endophthalmitis after cataract surgery" written by Guo et al in this issue. With recent advanced vitrectomy techniques, and critical measures for management of risk factors related to occurrence of infection, IOL remaining during timely vitrectomy for acute endophthalmitis can possibly be safe and effective in selected cases.

Vitreous function and intervention of it with vitrectomy and other modalities.

The vitreous body, the largest intraocular component, plays a key role in eye development, refraction, cell barrier function, oxygen metabolism and the pathogenesis of assorted diseases. Age, refraction and systemic diseases can cause vitreous metabolic abnormalities. With the continuous development of vitrectomy techniques and equipment, vitreous injections and vitrectomies have increased over the recent decades. However, the normal oxygen tension gradient in the vitreous helps to protect the lens and anterior chamber angle from oxidative stress damage, whereas the increased vitreous oxygen tension around lens and the trabecular meshwork after vitrectomy. It may lead to postoperative nuclear cataract and increase the risk for glaucoma. As a conventional procedure, scleral buckling holds several advantages over vitrectomy in selected cases. This review raises concerns regarding the function of the vitreous and encourages conducting vitreous interventions prudently if it is possible.

Long-term outcomes of drusenoid pigment epithelium detachment in intermediate AMD treated with 577 nm subthreshold micropulse laser: a preliminary clinical study.

AIM: To evaluate the long-term anatomical and visual outcomes of drusenoid pigment epithelial detachment (D-PED) in intermediate age-related macular degeneration (AMD) eyes treated with 577 nm yellow subthreshold micropulse laser (SML). METHODS: In this retrospective study, 21 eyes of 16 patients with D-PED in intermediate AMD were consecutively included and assessed. All the eyes were treated with 577 nm SML in several sessions according to D-PED growth status. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) were assessed at the initial visit and after treatment. Spectral-domain optical coherence tomography (SD-OCT) was performed to evaluate the D-PED lifecycle by volumetric calculations. Regression analysis was used to determine the breakpoint, growth, and collapse rate of the D-PED lesions. The progression to advanced AMD was also documented. RESULTS: All the eyes were treated with SML for 2.9±1.0 sessions. The mean follow-up period was 25.3±12.6mo. The BCVA was stable from the baseline to final visit. All the eyes were categorized into two groups according to the anatomical changes of the D-PED lesion: the collapse group (n=6, 28.6%) and non-collapse group (n=15, 71.4%). The change in logMAR BCVA did not differ significantly between the collapse group 0.00 (-0.31, 0.85) and non-collapse group 0.00 (0.00, 0.00; P=1). Regression analysis showed that the growth rate was significantly higher in the collapse group (0.090±0.095 mm3/mo) than in the non-collapse group (0.025±0.035 mm3/mo; P<0.001). One eye (4.8%) developed macular neovascularization at 11mo after SML treatment in the non-collapse group. Three eyes (14.3%) developed geographic atrophy (GA) in the collapse group. CONCLUSION: Compared to the natural course of D-PED reported by previous studies, our results preliminarily show that SML can alleviate visual loss and possibility of progression to advanced AMD in eyes with D-PED in intermediate AMD. A controlled clinical trial needs to further verify the benefit of the intervention.

Integrin ß1 subunit signaling is involved in the directed migration of human retinal pigment epithelial cells following electric field stimulation.

AIMS: Direct current electric fields (EFs) can induce directed cell migration in a wide variety of cells, and this has been proven to be of importance in wound healing. Here we observed the effects of EFs on cultured human retinal pigment epithelial (RPE) cells and explored the possible involvement of integrin ß1 subunit signaling in the process. METHODS: Cultured human RPE cells were exposed to an EF at 5 V/cm for 3 h. The rate and directionality of cell migration were quantified. The distribution of integrin ß1 subunit was measured by immunohistochemistry and the expression of integrin ß1 subunit and phosphorylated focal adhesion kinase (FAK) was determined by PCR and Western blotting. Experiments were performed in the presence or absence of anti-integrin ß1 subunit antibody. RESULTS: During exposure to an EF at 5 V/cm for 3 h, the separated human RPE cells and wounded RPE monolayer demonstrated a cathodal-directed migration. The distribution of integrin ß1 subunit in the cells was also polarized to the cathode, and the expression in mRNA and its protein level were obviously increased. Furthermore, exposure to EFs of 5 V/cm triggered the phosphorylation of FAK in human RPE cells. In contrast, blocking of integrin ß1 subunit suppressed the directed migration of RPE cells and reduced the activation of FAK in EFs. CONCLUSIONS: These findings indicate that EF exposure results in directed migration of the separated RPE cells and RPE monolayer. These effects may partially act through the activation of integrin ß1 subunit signaling.

Vitreous function and intervention of it with vitrectomy and other modalities.

The vitreous body, the largest intraocular component, plays a key role in eye development, refraction, cell barrier function, oxygen metabolism and the pathogenesis of assorted diseases. Age, refraction and systemic diseases can cause vitreous metabolic abnormalities. With the continuous development of vitrectomy techniques and equipment, vitreous injections and vitrectomies have increased over the recent decades. However, the normal oxygen tension gradient in the vitreous helps to protect the lens and anterior chamber angle from oxidative stress damage, whereas the increased vitreous oxygen tension around lens and the trabecular meshwork after vitrectomy may lead to postoperative nuclear cataract and a high incidence of open angle glaucoma. As a conventional procedure, scleral buckling holds several advantages over vitrectomy in selected cases. This review raises concerns regarding the function of the vitreous, and encourages conducting vitreous interventions prudently.

Newly-found functions of metformin for the prevention and treatment of age-related macular degeneration.

Metformin (MET), a first-line oral agent used to treat diabetes, exerts its function mainly by activating adenosine monophosphate-activated protein. The accumulation of oxidized phospholipids in the outer layer of the retina plays a key role in retinal pigment epithelium (RPE) cells death and the formation of choroidal neovascularization (CNV), which mean the development of age-related macular degeneration (AMD). Recent studies have shown that MET can regulate lipid metabolism, inhibit inflammation, and prohibit retinal cell death and CNV formation due to various pathological factors. Here, newly discovered functions of MET that may be used for the prevention and treatment of AMD were reviewed.

Commentary review on peripapillary morphological characteristics in high myopia eyes with glaucoma: diagnostic challenges and strategies.

The incidences of open angle glaucoma (OAG) and high myopia are increasing concomitantly. Considering the aging population and concurrent rapid increase in the number of individuals with myopia, the risk of visual defects caused by highly myopic OAG is likely to increase dramatically over the next few decades. However, precise screening and diagnosis of OAG is challenging because of the tilt and rotation of the optic disc, as well as extensive ß-zone parapapillary atrophy in highly myopic eyes. Recent advances in optical coherence tomography (OCT) and OCT angiography (OCTA) technologies imply that both modalities are promising tools for the detection of highly myopic OAG. Notably, the diagnosis of OAG remains to be determined with the longitudinal changes of functional damages (e.g. visual field defect, visual electrophysiological changes). We herein describe some aspects of microvascular and microstructural pathology in patients with highly myopic OAG and proposes a framework for the development of novel diagnostic and therapeutic strategies.

Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats.

PURPOSE: To explore the feasibility of bone marrow mesenchymal stem cells (MSCs) transdifferentiating into corneal epithelial cells in a limbal stem cell deficiency (LSCD) model in rats. METHODS: Rat MSCs were isolated and purified using a gradient isolation procedure. The cells were induced by rat corneal stromal cells (CSCs) in a transwell co-culture system. The induced MSCs were identified by immunofluorescence staining, flow cytometry, and scanning electron microscopy (SEM). A corneal LSCD model was produced in the right eyes of 48 rats by alkali injury. The eyes of 12 rats without any transplant served as controls (Group 1). Amniotic membranes (AM; Group 2), uninduced MSCs (Group 3), or MSCs induced by CSCs (Group 4), were transplanted onto the cornea of the model (n=12 each). The therapeutic effects of the four groups were evaluated by slit lamp observation, hematoxylin and eosin staining, immunohistochemistry staining, and confocal laser corneal microscopy. RESULTS: Cultivated MSCs were positive for CD29, CD44, and CD90, but negative for CD34, CD45, CD133, and CK12, with typical MSCs characteristics revealed by SEM. After co-culture with CSCs, the induced MSCs expressed positive staining for CK12 with corneal epithelial cell characteristics confirmed by SEM; the induced MSCs were unchanged on the amnion. Compared with the other three groups, the corneal opacity, fluorescence staining, and neovascularization grades were significantly decreased in the induced MSCs group, both on postoperative week four and ten. CONCLUSION: MSCs induced by CSCs can transdifferentiate into corneal epithelial cells in vitro. The induced MSCs on an amniotic membrane have remarkable effects on the treatment of corneal alkali burn and the reconstruction of the corneal surface of rats.

Inhibition of migration but stimulation of proliferation of human retinal pigment epithelial cells cultured with uniform vesicles of silicone oil.

BACKGROUND: It has been hypothesized that emulsification of silicone oil might stimulate preretinal membrane formation and proliferative vitreoretinopathy. This study aimed to test the effects of vesicles of silicone oil (VSO), which were prepared by a novel membrane emulsification technique, on the migration and proliferation of human retinal pigment epithelial (hRPE) cells in vitro. METHODS: VSO were produced by extrusion of the oil through a Supor membrane (Pall Life Sciences, Port Washington, NY, USA) with 0.45 microm pore size under a pressure of 0.1 MPa. hRPE cells were incubated with stained 25% VSO for 24 h to assess whether hRPE cells could phagocytize VSO. A wound-healing model was used by denuding cells from a glass slide to assess the migration of hRPE cells. The cells were then incubated with 25%, 50% and 100% VSO with or without serum for up to 72 h. The number of cells that had entered the denuded area was counted under a microscope. To assess the proliferative activity, the cells were incubated with 25%, 50% and 100% VSO, with or without serum, for 24 h. A total of 100 nuclei were examined for each slide, and the numbers of stained argyrophilic nucleolar organizer regions (AgNORs) in the nuclei were measured. RESULTS: The mean vesicle diameter of VSO prepared was 4.25 +/- 0.77 microm. The stained 25% VSO were phagocytized by hRPE cells. After the cells cultured with serum-free Dulbecco's Modified Eagle Medium (DMEM) were incubated with VSO, the numbers of migratory cells at higher concentrations (50% and 100%) of VSO were significantly decreased (48.9 +/- 5.37 and 10.6 +/- 3.03 respectively) compared to controls (69.9 +/- 9.88; P < 0.01). After the cells cultured with serum-free DMEM were incubated with VSO, the number of AgNORs in nucleus at 100% VSO was significantly increased compared to controls (3.1 +/- 0.72 vs 1.6 +/- 0.6; P < 0.01). CONCLUSION: The result indicated that VSO inhibited the migration but stimulated the proliferation of hRPE cells.

[Management pattern of diabetes mellitus and prevention and control of diabetic retinopathy].

The Bureau of Disease Prevention and Control, National Ministry of Health, recently released a project for the management of diabetes mellitus along with a technical operational manual. This is a landmark event in the prevention and management of ocular fundus diseases in China. This project will be carried out through collaboration of general hospitals, community health service units, and disease prevention and control organizations. It provides an excellent platform for the prevention and control of diabetic retinopathy. In order to prevent and control this disease, we should follow the patient-centered principle, which includes establishing individual health files, providing consultation for patients, performing screening of diabetic retinopathy, and providing lifelong regular examinations, follow-up and prompt treatments. We should also insist on the combination of prevention, treatment and scientific study to take advantage of a wide array of population resources for studying the pathogenesis and risk factors involved in the development of diabetic retinopathy, and making new contributions in the prevention of blindness due to diabetes.