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Retinal neurodegeneration is an early feature in the pathogenesis of diabetic retinopathy (DR). Autophagy is an intracellular catabolic process involved in protein and organelle degradation that has been linked in DR. Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in diabetic. however, it is not currently known whether EGCG can regulate Müller cell autophagy. Here, we showed that EGCG increased autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, and stimulating autophagic flux in Müller cells, while high glucose (HG) induced a decrease in autophagy and an increase in apoptosis. However, retinal Müller cells in HG treated with EGCG showed autophagy machinery activation and reestablishment of cargo degradation, protecting the cells from apoptosis. EGCG could increase the ability of cells to proliferate by increasing autophagy. In an experimental model of diabetic retinopathy, EGCG reduced the reactive gliosis of Müller cells and decreased retinal damage. These results highlight that HG downregulates autophagy and accumulates P62 cargo due to lysosomal dysfunction and then increases apoptosis, which was reversed by treatment with EGCG. This finding might be valuable for developing a novel therapeutic strategy to treat DR. • This experimental drug EGCG is a natural component of green tea. • EGCG induced cell proliferation and decrease apoptosis in Müller cell. • EGCG enhanced autophagic flux through regulating mTOR mediated pathway in HG-treated Müller cells. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a leading cause of severe vision impairment in the aging population. However, the underlying molecular mechanism remains unclear. Ferroptosis is a novel non-apoptotic programmed cell death pathway, that contributes to AMD. In addition, non-coding RNA-led epigenetic profile was identified in the regulation of AMD progression. Considering that non-coding RNAs are vital regulators of ferroptosis-related genes in various pathological events, we explored and constructed a ferroptosis-associated circRNA-miRNA-mRNA network in AMD. Differential expression of fourteen ferroptosis-associated genes were identified based on our microarray analysis and the FerrDb tool at the threshold of P < 0.05 and log 2 |fold change| ≥ 1, which were subsequently validated by the public datasets. We further screened eight miRNAs via public datasets and the miRNet database. Based on these eight miRNAs, 23 circRNAs were mined using the Starbase tool. Taking all these together, we obtained a ferroptosis-related network with 414 pairs of circRNA-miRNA-mRNA, which are potential targets in future AMD treatments. • Differentially expressed genes (DEGs) in microarray analysis were intersected with ferroptosis related genes to identify promising ferroptosis-associated DEGs in CNV. • Potential circRNAs and miRNAs were mined and validated via public datasets and online tools. • A ferroptosis-associated circRNA-miRNA-mRNA network with 14 ferroptosis-associated genes, 8 miRNA and 23 circRNAs in CNV etiology was constructed for the first time, to our knowledge. [ABSTRACT FROM AUTHOR]

Highlights: [•] DIMEN displays higher anti-proliferative activity than enastron. [•] DIMEN induced mitotic arrest and apoptosis more significantly than enastron. [•] DIMEN blocked the conformational change of ADP-binding pocket more effectively. [•] DIMEN hindered ADP release more potently than enastron. [ABSTRACT FROM AUTHOR]