Resveratrol ameliorates early retinal neurodegeneration in diabetic retinopathy via microRNA-29b/specificity protein 1/apoptosis pathway by enhancing autophagy

Abstract Therapeutic targeting of retinal Müller cells (RMCs) has garnered tremendous attention for early prevention and treatment of diabetic retinopathy (DR). The microRNA-29b (miR-29b)/specificity protein 1 (SP1) pathway is critical for RMCs survival in hyperglycemic environments, and miR-29b downregulation and SP1 upregulation contribute to RMCs apoptosis during early DR stages. Resveratrol (RSV), a natural plant polyphenol, can inhibit RMCs apoptosis by regulating miR-29b/SP1 expression, playing an important role in early DR protection. However, how RSV affects high-glucose-stimulated miR-29b downregulation and SP1 upregulation in early DR remains poorly understood. Here, we show that RSV increased autophagosome formation and LC3-I/LC3-II and Beclin-1 levels while decreasing P62 level, thereby promoting autophagy and inhibiting dysregulation of miR-29b/SP1 pathway expression and RMCs apoptosis in DR rat retinal tissues and high glucose-cultured RMCs. This is supported by findings that autophagy inducer rapamycin (RAPA) enhances the effect of RSV on inhibiting high-glucose-induced dysregulation of miR-29b/SP1 expression and apoptosis of RMCs in DR rat retinal tissues and high glucose-cultured RMCs. Inhibition of autophagy with 3-methyladenine (3-MA) attenuates the effect of RSV on inhibiting high-glucose-induced dysregulation of miR-29b/SP1 expression and apoptosis of RMCs in DR rat retinal tissues and high glucose-cultured RMCs. In summary, these results suggest that RSV further inhibits the apoptosis of RMCs by activating autophagy and regulating the early miR-29b downregulation and SP1 upregulation induced by high glucose, thereby inhibiting the progression of DR. Our findings suggest that RSV has great potential in the early prevention and treatment of DR.