PG545 alleviates diabetic retinopathy by promoting retinal Müller cell autophagy to inhibit the inflammatory response.

Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Müller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly reduced diabetes-induced body weight changes and fasting blood glucose levels in mice. PG545 also mitigated the reduction in retinal thickness and the formation of microaneurysms by promoting autophagy to inhibit the inflammatory response. In vitro, PG545 stimulated autophagy to downregulate the inflammatory response in high glucose-induced primary adult mouse RMCs. These data suggest that PG545 mitigates DR by promoting RMC autophagy to inhibit the inflammatory response.

Prodrug of epigallocatechin-3-gallate alleviates choroidal neovascularization via down-regulating HIF-1α/VEGF/VEGFR2 pathway and M1 type macrophage/microglia polarization.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly and is attributed to choroidal neovascularization (CNV), which is a feature of wet AMD. The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway contributes to the pathogenesis of CNV. M1-type macrophages/microglia secrete interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), facilitating the development of CNV. Epigallocatechin-3-gallate (EGCG) is a kind of polyphenol in green tea that exerts anti-inflammatory and antiangiogenic effects. In this study, a prodrug of EGCG (pro-EGCG) alleviated mouse laser-induced CNV leakage and reduced CNV area by down-regulating HIF-1α/VEGF/VEGFR2 pathway; M1-type macrophage/microglia polarization; as well as endothelial cell viability, proliferation, migration and tube formation, indicating a novel potential therapy for AMD.

LncRNA FEZF1-AS1 Promotes TGF-ß2-Mediated Proliferation and Migration in Human Lens Epithelial Cells SRA01/04.

Posterior capsule opacification (PCO) is a common complication after cataract surgery attributed to the proliferation and migration of postoperative residual lens epithelial cells (LECs). The long noncoding RNA (lncRNA) FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) promotes the proliferation and migration of multiple types of cancer cells. Here, we discovered that FEZF1-AS1 is markedly upregulated in TGF-ß2-treated SRA01/04 cells. In addition, the proliferation and migration of SRA01/04 cells were enhanced following TGF-ß2 treatment. FEZF1-AS1 knockdown inhibited the TGF-ß2-induced proliferation and migration of SRA01/04 cells. Accordingly, FEZF1-AS1 overexpression promoted the TGF-ß2-induced proliferation and migration of SRA01/04 cells. Finally, FEZF1-AS1 upregulated TGF-ß2-induced SRA01/04 cell proliferation and migration via boosting FEZF1 protein levels. Our findings indicate that the dysregulation of FEZF1-AS1 participates in the TGF-ß2-induced proliferation and migration of human lens epithelial cells (HLECs), which might be achieved, at least in part, through the induction of FEZF1 expression.