Role of regulatory T cells in modulating corneal neovascularization in a murine model of diabetes.

Abstract

Diabetes mellitus (DM) disrupts immune regulation and promotes pathological angiogenesis, including corneal neovascularization (CNV), which threatens vision. Regulatory T cells (Tregs), known for their immunosuppressive properties, have context-dependent effects on angiogenesis, yet their function in the ocular tissues of diabetic patients, remains unclear. In this study, we evaluated Treg-mediated modulation of CNV in a murine model of DM using suture-induced neovascularization. Compared to controls, diabetic mice exhibited significantly exacerbated CNV, as assessed by clinical scoring and CD31 immunostaining. In vitro co-culture assays revealed that while normal Tregs suppressed vascular endothelial cell (VEC) tube formation, diabetic Tregs lacked this inhibitory capacity. Subconjunctival delivery of normal, but not diabetic, Tregs suppressed CNV in vivo. Mechanistically, diabetic Tregs demonstrated significantly elevated IL-10 expression, a cytokine implicated in pro-angiogenic signaling. Neutralization of IL-10 in vitro restored the anti-angiogenic function of diabetic Tregs in a dose-dependent manner. Furthermore, adoptive transfer of IL-10 knockout Tregs significantly inhibited CNV in diabetic mice, and diabetic IL-10 KO mice exhibited reduced vascularization compared to wild-type diabetic controls. These findings identify a novel IL-10-mediated dysfunction in diabetic Tregs and highlight a potential therapeutic strategy targeting IL-10 signaling to restore immune-mediated suppression of corneal neovascularization in diabetes. This approach may improve clinical outcomes in diabetes patients following injury, infection and high-risk corneal transplantation.