PRDX2 and Müller cells in diabetic retinopathy

Abstract

A possible new and different focus on diabetic retinopathy, particularly on neuroglial pathways, was proposed by Du et al in their article published in the World Journal of Diabetes. By measuring biomarker levels in vitro and in vivo, the authors highlighted the relationship between peroxiredoxin-2 (PRDX2) levels and diabetic retinopathy severity and reported that PRDX2 levels were independently associated with proliferative disease, thereby attributing to PRDX2 a role beyond that of angiogenic markers. High PRDX2 levels were found in human diabetic tissues and murine models, specifically in Müller glial cells and in glial cultures stimulated with a glucose-rich environment. The fundamental role of PRDX2 in Müller cell hyperreactivity, proliferation, and cytoskeletal remodeling was also confirmed by PRDX2 knockdown experiments. Gliotic transformation is stimulated by redox stress and is linked to activation of the RhoA/ROCK pathway through the loss of RhoGDI1-mediated inhibition. This study challenges conventional antioxidant paradigms and introduces new opportunities for neuroglia-centered treatment approaches in diabetic retinopathy.

Keywords: Müller glial cells; Diabetic retinopathy; RhoA/ROCK signaling; Peroxiredoxin-2; Redox dysregulation

Core Tip: The emerging role of Müller cell dysfunction in anticipating and worsening diabetic retinopathy is increasingly acknowledged. The altered redox balance in Müller glial hyperreactivity that triggers the RhoA/ROCK pathway was extensively demonstrated by Du et al through peroxiredoxin-2 (PRDX2). This article reviews PRDX2-related cytoskeletal reorganization and glial proliferation. It also offers a perspective that extends beyond the conventional role of antioxidant enzymes and identifies potential targeted therapies to counteract gliosis and preserve neurovascular health.