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AIM: To investigate therapeutic effects of traditional Chinese medicine formulations, Hexuemingmu (HXMM) on laser-induced choroidal neovascularization (CNV) and follow-up effect in mice. METHODS: C57BL/6 mice of 8-week-old were used and CNV was induced with 577 nm laser photocoagulation. Animals were randomly divided into groups and different doses of HXMM were administered daily. One, four, and eight weeks after the intervention, the electroretinogram (ERG), fundus fluorescence angiography, choroidal flat mount and immunofluorescence staining were preformed to evaluate the function and CNV formation. The expression levels of angiogenic proteins were determined by Western blotting and immunofluorescence staining. An analysis of variance and Kruskal-Wallis test were used to test the differences among the groups. RESULTS: The results showed that HXMM effectively increased amplitude of ERG of mice (P

To investigate the influence of age on the function and morphology of patients with myopic choroidal neovascularization (mCNV) and to evaluate the effect and prognostic factors of recurrence of Conbercept treatment on mCNV patients over 50 years. A total of 64 patients (64 eyes) with mCNV were enrolled in this retrospective study. The differences in baseline best-corrected visual acuity (BCVA) and morphological features on imaging between the younger group (˂ 50 years) and the older group (≥ 50 years) were analyzed. Of all, 21 eyes of 21 mCNV patients aged over 50 years who received Conbercept injection were further analyzed. Between the younger and the older group, significant differences were shown in mean BCVA (0.58 ± 0.28 vs 0.77 ± 0.31), subfoveal choroidal thickness (SFCT) (108.17 ± 78.32 μm vs 54.68 ± 39.03 μm) and frequency of vitreoretinal interface abnormalities (VIA) (2 vs 13), respectively (P

Purpose: The aim of this study is to explore the clinical features of spontaneous regression of retinopathy of prematurity (ROP) in China, including fundus appearance, time course, and affecting factors.Methods: Data of pediatric patients in whom ROP spontaneously regressed without treatment were collected, including general demographics, medical history, zones and stages of ROP, and changes of fundus appearance. The fundus manifestations of spontaneous regression in ROP were systematically summarized. Meanwhile, the time course of spontaneous regression in ROP was further analyzed, including the onset time, completion time, and duration of regression, which were all compared across different ROP zones and stages. The associated factors were analyzed by survival analysis for their correlation with delayed regression for the first time.Results: Two hundred thirty-seven eyes of 237 pediatric patients were included. The fundus manifestations of regression differed across stages. Lesions gradually subsided, and the retinal vessels gradually vascularized completely. However, despite ROP regression, some abnormalities remained. We observed avascular retina in the temporal periphery (19.0%), increased vascular branching (6.8%), retinal pigmentary changes (6.8%), and smaller angle between the upper and lower temporal retinal vessel trunks (3.0%). Acute ROP started to regress at a median 40 weeks of postmenstrual age (PMA) and completely regressed by median 49.0 weeks of PMA. The median duration for regression was 8.5 weeks. The zone II ROP and stage 3 ROP had a later time for onset and completion of regression, and longer duration. Anemia and retinal hemorrhage (RH) were identified as independent risk factors for delayed regression by survival analysis.Conclusions: During spontaneous regression, the fundus appearance is diverse, and the retinal vessels gradually vascularized completely. The time course of regression differs depending on the ROP zone and stage. Anemia and RH are independent risk factors for delayed regression. Further research of the natural course of the regression of ROP is needed to help design effective screening and follow-up plans.

Choroidal neovascularization (CNV) is an acknowledged pathogenic mechanism of various ocular diseases, and in situ cells and mobilized bone marrow-derived cells (BMCs) are thought to participate in this process. We aimed to evaluate the roles of integrin α5 in BMCs and vascular endothelial cells (VECs) in the CNV process mediated by SDF-1/CXCR4 signaling. Adult wild-type mice were engrafted with whole BMCs obtained from GFP transgenic mice and then laser injured to induce CNV. BMCs and RF/6A cells were cultured to discover the mechanism of CNV in vitro. BMCs were mobilized to CNV areas, which expressed elevated SDF-1 and CXCR4. When SDF-1 was intravitreally injected, the number of BMCs was profoundly increased. In the SDF-1-treated group, the levels of integrin α5 expressed on BMCs and VECs were significantly higher than those on the cells in the control group. SDF-1 significantly increased the expression and positive ratio of integrin α5, which was involved in the recruitment and differentiation of BMCs into BMC-derived VECs, and these effects were suppressed by the CXCR4 inhibitor AMD3100. The PI3K/AKT pathway rather than the ERK pathway mediated SDF-1/CXCR4 induction of integrin α5. Integrin α5 suppression efficiently prevented the production of TGF-β and bFGF but not VEGF. Inhibiting the SDF-1/CXCR4-PI3K/AKT-integrin α5 axis reduced CNV severity. Integrin α5 participates in BMC recruitment and differentiation in SDF-1/CXCR4-induced CNV and inhibition of this pathway may be a new approach to inhibit CNV.

Background: Oxidative stress (OS) is an essential factor in the pathogenesis of branch retinal vein occlusion (BRVO). Lines of studies have demonstrated the role of hydrogen gas in the regulation of OS. This study was designed to evaluate the effect of hydrogen gas on BRVO rat model which was established by modified laser photocoagulation method. Methods: 24 BRVO rats were randomly divided into two groups: hydrogen gas (H) group (42% H2, 21% O2, 37% N2) and model (M) group (21% O2, 79% N2). Rats in H group were inhaled with hydrogen gas for 8 hours every day continued to 30 d post-occlusion. 12 age-matched healthy rats were served as control (C) group. Retinal function and morphology were detected at 1, 7, 14 and 30 d post-occlusion. Furthermore, the expression of vascular endothelial growth factor (VEGF-α) was detected by immunofluorescent staining. Results: Full-field Electroretinography (FfERG) revealed that the amplitude of the d3.0 (dark-adaptation 3.0 response) b wave and OPs2 (oscillatory potentials) wave achieved quick recovery at 7 d post-occlusion in H group compared with M group (p<0.05; pppppp>0.05). Conclusions: Our findings demonstrate that inhalation of hydrogen gas could alleviate retina edema, shorten reopen time and improve retinal function via decreasing VEGF-α expression. Key words: Hydrogen gas; branch retinal vein occlusion; electroretinography; vascular endothelial growth factor

Background Severe retinopathy of prematurity (ROP) with extremely unfavorable prognosis among infants can do great damage to individuals and bring tremendous social-economic burden. The purpose of this study is to describe the demographic and ocular characteristics of infants who presented with stage 5 ROP in order to identify reasons why they have become blind, and to identify contributing factors in order to focus great attention on the current ROP program and to inspire more effort in ROP screening in middle income countries. Methods A retrospective review of consecutive infants with stage 5 ROP from December 2010 to December 2016 in Department of Ophthalmology, Xijing Hospital. Various parameters retrieved included birthweight, gestational age, age at initial examination, postmenstrual age, screening details, check-up details and reasons for consultation. Ocular findings were recorded and also detected by ultrasonography. Results A retrospective review of 20 consecutive infants with stage 5 ROP are included. Mean birthweight was1712.3 ± 512.97 g and mean gestational age at birth was 32.1 ± 2.21 weeks. Median age at first consultancy was 9.7 month. Median postmenstrual age first consultancy was 52 weeks. All infants were never screened for ROP before they came to the referral center. Of twenty stage 5 ROP infants, 13 cases presented with bilateral stage 5 features. Of the 40 eyes of 20 infants, 33 eyes were diagnosed as stage 5. Leukocoric pupil, closed funnel configuration of retinal detachment (RD), posterior synechia, extraretinal fibrovascular proliferation and retinal folds were the most significant indicators of bad prognosis. Ten eyes appeared no fixation to light, while 30 eyes exhibited following to light or following to toys. Conclusions Our study shows that in relatively less-developed regions of China, more needs to be done to spread awareness about the disease among pediatricians, neonatologists and ophthalmologists as well as parents of premature infants. Thus, a comprehensive control system which is a whole network of propaganda, screening, treatment and follow-up are encouraged especially in less developed areas in China as well as worldwide.

Our previous investigations have shown that bone marrow-derived cells (BMCs), including mesenchymal stem cells (MSCs), contribute to the development of choroidal neovascularization (CNV) as sources of cells and angiogenic factors. Two main steps for circulating BMCs to integrate into CNV lesions are extracellular matrix remodeling and consequential cell migration. MicroRNAs (miRNAs) were found to be involved in CNV development; however, little is known about whether miRNAs regulate the contribution of BMCs to CNV. In the present study, we found that the expression of miR-188-5p was decreased in cultured hypoxic MSCs and BMCs within laser-induced CNV in mice. Matrix metalloproteinase 2 (MMP-2) and MMP-13 were both discovered as targets of miR-188-5p by bioinformatics predictions and dual-luciferase reporter system. Accordingly, increased expression of MMP-2/13 was found in hypoxic MSCs and BMCs in CNV lesions. Furthermore, miR-188-5p mimic transfection caused downregulation of MMP-2/13 in hypoxic MSCs and decreased tube formation of co-cultured vascular endothelial cells. Intravitreal injections of a miR-188-5p agomir attenuated the severity of CNV and inhibited the migration of BMCs into CNV lesions in mice. Our study suggests that miR-188-5p regulates the contribution of BMCs to CNV development by targeting MMP-2/13-mediated extracellular matrix degeneration, and miR-188-5p serves as a therapeutic target to treat CNV-related diseases.