GSTP1 expression mitigates endothelial dysfunction in diabetic retinopathy through regulation of oxidative stress:...

Diabetic retinopathy (DR) remains a major microvascular complication of diabetes, with substantial global variations in prevalence and severity. This study aimed to investigate alterations in the immune microenvironment of diabetic retinopathy and explore key regulatory mechanisms in endothelial cells.

We analyzed immune microenvironment differences between DR and non-DR samples using single-cell sequencing data. Key modules and genes in endothelial cells were identified through hdWGCNA analysis. The expression of GSTP1 and its effects on apoptosis and reactive oxygen species (ROS) were validated in a DR endothelial cell model.

Single-cell analysis revealed significantly decreased T cell populations in DR patients with notable differences in endothelial cell profiles between groups. Further examination of endothelial cells demonstrated upregulation of metabolic pathways and major histocompatibility complex (MHC) functions in DR patients. Notably, GSTP1 was identified as a significantly downregulated gene in DR. In the in vitro DR endothelial cell model, GSTP1 overexpression significantly increased cell viability, while decreasing apoptosis and ROS accumulation.

This study identifies an altered immune microenvironment in diabetic retinopathy (DR), characterized by T-cell decrease and upregulated endothelial cell pathways. The key finding is that the low expression of GSTP1 impairs endothelial antioxidant capacity, while its overexpression mitigates apoptosis and oxidative stress, underscoring its protective role in DR. These results position GSTP1 as a promising therapeutic target for intervening in DR progression.

Our findings provide novel insights into GSTP1's role in DR pathogenesis and offer theoretical support for developing GSTP1-based therapeutic strategies for diabetic retinopathy.