Overexpression of microRNA-130a-3p suppresses glucose lipid levels and oxidative damage in diabetic retinopathy mice via modulating cell division cycle 42.

MicroRNA (miR)-130a-3p has been unraveled to exert effects on diabetes. However, the research for probing its role in diabetic retinopathy (DR) is limited. Our study intends to unravel the regulatory effects of miR-130a-3p on DR development via cell division cycle 42 (CDC42). The DR mouse model was established and the serum sample of DR patients was collected. The levels of miR- 130a-3p and CDC42 in DR mice and patients were detected. The nucleic acids modified miR-130a-3p or CDC42 were injected into DR mice to examine the change of glucose lipid levels, visual acuity, oxidative response and the distribution and expression of CDC42 in retinal tissues in DR mice. The target relationship between miR-130a-3p and CDC42 was confirmed. MiR-130a-3p expression was reduced while CDC42 levels were elevated in DR (P<0.05). The upregulation of miR-130a-3p could hinder glucose lipid levels, improve the visual acuity, relieve the oxidative response and decrease CDC42 expression levels in DR mice (P<0.05). The CDC42 elevation reversed the positive effects of upregulated miR-130a-3p on DR progression (P<0.05). MiR-130a-3p targeted CDC42. The elevated miR-130a-3p relieves glucose lipid levels and oxidative damage in DR by modulating CDC42. The study provides novel therapeutic targets for DR treatment.

A novel miR-338-3p/SLC1A5 axis reprograms retinal pigment epithelium to increases its resistance to high glucose-induced cell ferroptosis.

BACKGROUND: Oxidative stress-induced cell ferroptosis occurs during the pathogenesis of diabetic retinopathy (DR), but the detailed molecular mechanisms are still unclear. The present study aimed to investigate this issue. MATERIALS AND METHODS: The retinal pigment epithelium (RPE) was treated with high glucose (30 mM) in vitro to mimic the realistic conditions of DR progression in vivo. Cell viability was determined by MTT assay and trypan blue staining assay. Gene expressions were examined by Real-Time qPCR and Western Blot analysis. FCM was used to detect cell apoptosis and ROS generation. Dual-luciferase reporter gene system assay was used to verify the targeting sites. RESULTS: High glucose increased reactive oxygen species (ROS) levels, promoted cell ferroptosis, and suppressed cell proliferation and viability in RPE, which were reversed by co-treating cells with both a ferroptosis inhibitor ferrostatin-1 and an ROS scavenger, N-acetyl-L-Cysteine (NAC). In addition, we screened out a miR-338-3p/ASCT2 (SLC1A5) axis that played an important role in this process. Mechanistically, miR-338-3p targeted the 3' untranslated regions (3'UTR) of SLC1A5 for its inhibition and degradation, and high glucose downregulated SLC1A5 by upregulating miR-338-3p in RPE cells. Next, the miR-338-3p inhibitor and SLC1A5 overexpression vectors were delivered into the RPE cells, and the following gain- and loss-of-function experiments validated that both miR-338-3p ablation and SLC1A5 upregulation abrogated the regulating effects of high glucose on cell proliferation, viability, ferroptosis and ROS production in RPE cells. CONCLUSIONS: Collectively, data in the present study indicated that targeting the miR-338-3p/SLC1A5 axis could block high glucose-induced ferroptosis in RPE cells.

Effects of Novel Anti-VEGF Agents with Intravitreal Conbercept in Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

To evaluate the efficacy and safety of intravitreal conbercept (IVC) for diabetic retinopathy (DR) compared with intravitreal triamcinolone acetonide (IVTA). PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their earliest records to January 2020. We included randomized controlled trials (RCTs) evaluating the efficacy and safety of conbercept in DR patients compared with ITVA. Outcomes included the mean changes from the baseline in best corrected visual acuity (BCVA) score, central macular thickness (CMT), quality of life (QoL) over time, and the incidence of adverse events (AEs). A total of 19 RCTs involving 1,811 eyes were included in this meta-analysis. IVC might improve BCVA (WMD = 0.10, 95% CI (0.07, 0.12), P < 0.001) and reduce CMT (WMD = -102.5, 95% CI (-148.48, -56.53), P < 0.001) compared to IVTA. The incidence of AEs in patients receiving IVC was significantly lower than those receiving IVTA (RR = 0.29, 95% CI (0.21, 0.40), P < 0.001). Patients with IVC treatments acquired better self-care, mobility, social, and mental scores compared with IVTA (P < 0.001). Current evidence shows that IVC has better effects and safety than IVTA in treating DR, and it can significantly enhance the QoL of patients with DR.

Comparison of bevacizumab and ranibizumab in age-related macular degeneration: a systematic review and meta-analysis.

AIM: To compare the effectiveness and safety between bevacizumab and ranibizumab in the treatment of age-related macular degeneration (AMD) through a systematic review and meta-analysis. METHODS: We performed a comprehensive search of randomized controlled trials (RCTs), non-RCTs, case-control and cohort studies that compared bevacizumab and ranibizumab using PubMed and the Cochrane Library. After the related data were extracted by two investigators independently, pooled weighted mean differences (WMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects or a fixed-effects model. RESULTS: A total of four RCTs involving 1927 patients and eleven retrospective case series involving 2296 patients were included. For the primary outcomes, no significant differences were found between ranibizumab group and bevacizumab group in visual acuity (WMD: -0.04; 95%CI: -0.08 to 0.00; P=0.06), best corrected visual acuity (WMD: -0.05; 95%CI: -0.10 to 0.00; P=0.05), retina thickness (WMD: -4.69; 95%CI: -13.15 to 3.76; P=0.86) and foveal thickness (WMD: 10.91; 95%CI: -14.73 to 36.56; P=0.40). The pooled analyses in the evaluation of safety showed that compared to bevacizumab, ranibizumab was associated with decreased risks of ocular inflammation (RR: 0.45; 95% CI: 0.23 to 0.89; P=0.02) and venous thrombotic events (RR: 0.27; 95%CI: 0.08 to 0.89; P=0.03). However, there were no significant differences observed in deaths (P=0.69) and arterial thromboembolic events (P=0.71) between the two groups. CONCLUSION: With equal clinical efficacy, ranibizumab was found to be associated with less adverse events compared to bevacizumab, indicating that ranibizumab might be a safer management.