Overexpression of Brg1 alleviates high glucose-induced retinal ganglion cell apoptosis though regulating Notch/Hes1 signaling

Abstract

High glucose (HG)-caused damage of retinal ganglion cells (RGCs) plays an important role in the pathogenesis of diabetic retinopathy, a common and severe complication of diabetes mellitus. Accumulating evidence has reported that brahma-related gene 1 (Brg1) exerts a cytoprotective role in protection of cells from various injuries. In this study, we investigated the role of Brg1 in regulating HG-induced injury of RGCs. We found that RGCs treated with HG exhibited a low expression level of Brg1 compared with untreated RGCs. Gain-of-function experiments showed that Brg1 overexpression significantly improved the viability and reduced the apoptosis of RGCs exposed to HG. Notably, our data revealed that Brg1 overexpression increased the expression of Notch ligands, including Jagged 1, Jagged 2, Delta-like 1, and Delta-like 4. Moreover, Brg1 overexpression upregulated the expression of Notch1 intracellular domain (NICD) and Hes1, which resulted in activation of Notch signaling. Blockade of Notch signaling partially reversed Brg1-mediated protection effect in HG-treated RGCs, while overexpression of NICD significantly attenuated the promotion effect of Brg1 silencing on HG-induced injury in RGCs. Taken together, these results suggest that Brg1 protects RGCs against HG-induced injury through enhancing the activation of Notch signaling, suggesting a potential target for preserving RGCs in diabetic retinopathy.