Human aging is a multifactorial process. The most prominent effects of aging include visual impairments, particularly age‑related cataracts (ARC). Several studies have reported that oxidative stress and failure of the antioxidant system are the major factors contributing to lens oxidation. The present study focused on the nuclear factor erythroid 2‑related factor 2 (Nrf2)/kelch‑like ECH‑associated protein 1 (Keap1)‑mediated antioxidant system and its failure in aging lenses. The protein levels, gene expression and methylation status of Nrf2/Keap1 were investigated in human lenses from different age groups. Human lens epithelial cells were collected from different age groups ranging between 15 and 80 years and cataract lenses were also collected for the comparative study. The results demonstrated significantly lower protein and gene expression levels of Nrf2 in lenses of increasing age; however, a significant increase in the expression of the Nrf2 regulator, Keap1, was observed. Based on these results, the present study then aimed to investigate the underlying mechanisms. A gene specific DNA methylation study was performed in cataractous lenses of different ages, which revealed significantly increased levels of demethylated DNA in the Keap1 promoter with increasing age. Notably, the results from cataract lenses demonstrated significant demethylation of the Keap1 promoter, which was also reflected in the results of clear lenses aged between 66 and 80 years. These results suggested that demethylation in the Keap1 promoter region activated the expression of the Keap1 protein, which then increased the targeting of Nrf2 for proteasomal degradation. Therefore, decreased activity of Nrf2 restrained the transcription of its downstream antioxidant enzyme and led to the failure of the antioxidant system, ultimately leading to the formation of ARCs.

Purpose. To explore the effect of VEGF (vascular endothelial growth factor) on the vasculogenic mimicry (VM) formation of Choroidal Melanoma (CM) through PI3k signal pathway, to find novel targets for CM therapy. Methods. This research investigated the molecular mechanism of VEGF promoting VM formation of CM. First, we evaluated the expressions of VEGF in 20 CM specimens by immunohistochemical determination. Then we detected expressions of VEGF, AKT, MT1-MMP, MMP2, and MMP9 of OCM-1 in hypoxia. siRNA was used to inhibit the expression of VEGF, to realize the control of the VM formation. The VM formation was evaluated through wound healing assay, transwell assay, and apoptosis. And then we testify the correlation of the VM and the factors in protein and mRNA level preliminarily. Results. VEGF protein was expressed in CM in all 20 cases of CM, especially along the VM. In hypoxia, the expression of VEGF in OCM-1 increased significantly. VEGF gene deletion reduced the proliferation, migration, and invasion of OCM-1. VEGF gene deletion impaired the expression of invasive associated genes like VEGF, p-AKT, AKT, MT1-MMP, MMP2, and MMP9. These results indicate that VEGF induce VM formation in CM by activating PI3K/AKT signaling pathway. Conclusions. VEGF promoted VM formation by the PI3K signal transduction pathway, indicating a molecular mechanism which may be used to develop new therapeutic targets for the clinical treatment of CM.

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Background: To evaluate functional and anatomical consequences of switching anti-vascular endothelial growth factor (anti-VEGF) therapy from bevacizumab and/or ranibizumab to aflibercept intravitreal injection for the treatment of persistent diabetic macular edema (DME).Methods: Analysis of switching treatment in patients with persistent DME was performed using a literature search across multiple databases (PubMed, Medline, EMBASE, Cochrane Library and Web of Science) prior to May 2019. Therapeutic effect parameters, including mean change of best-corrected visual acuity (BCVA) and central macular thickness (CMT), were extracted from baseline to different follow-up times post initial injections. The quality of studies was assessed with the Downs and Black checklist. Data pertaining to ocular and systemic safety adverse events (SAEs) were collected as well as subgroup analysis stratified by preswitch anti-VEGF reagents. All results were analyzed and pooled using random-effects models with 95% confidence intervals (CI).Results: Fourteen studies involving 489 eyes met the inclusion criteria. The mean differences in BCVA were significantly improved at 1, 2 and 3 months with −0.11 logMAR (P=0.016), −0.22 logMAR (P<0.001) and −0.24 logMAR (P<0.01), respectively. Vision gain was also assessed following the aflibercept injection with a mean change of −0.10 logMAR (P<0.001) at 6 months and −0.08 logMAR (P=0.01) at 12 months.CMT reduction was significant from baseline with a mean decrease of 80.52 μm (P<0.001) at 1 month, 89.6 μm (P<0.013) at 2 months, 113.88 μm (P<0.001) at 3 months and 125.12 μm (P<0.001) at 6 months.Mean CMT continued to decline by 75.70 μm (P<0.001) at 12 months as well.Conclusions: This meta-analysis indicated the comparable efficacy and safety of a conversion treatment to aflibercept in cases of unsatisfactory responses to other anti-VEGF drugs. Switching treatment produces significant advantage for vision acuity recovery and macular edema improvement among persistent DME patients.

Rationale:Retinal cavernous hemangioma is a rare congenital vascular malformation with typical fundus changes. Optical coherence tomography angiography (OCTA), which is in rise in the recent years, is a rapid and noninvasive technology to assist in obtaining information regarding the blood flow changes in the fundus lesions from different layers without injecting a contrast agent.Patient concerns:A 40-year-old male patient with visual occlusion in the right eye for >1 month was reported.Diagnoses:Retinal cavernous hemangioma was diagnosed by fundus examination, fluorescein angiography (FA) and OCTA, and the characteristics of OCTA images were analyzed.Interventions:The lesion occurred outside the macula, the central vision remained basically normal, and no significant complications were noted in this patient. Therefore, we preferred to regularly follow-up without therapeutic intervention.Conclusions:OCTA can display fundus blood flow and vascular lesions noninvasively and rapidly. On OCTA, retinal cavernous hemangiomas showed characteristic changes and have good correspondence with fundus imaging and FA examinations. Moreover, OCTA remains more sensitive to vascular abnormalities, and imaging remains clearer, providing new diagnosis and follow-up route for this disease.

Polymer-based hydrogels used in the vitreous cavity could incur unsatisfactory gel-forming state, uncontrollable swelling, and potential cytotoxicity. Their application can significantly impair the filling effect and cause severe side effects...

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