Downregulation of MerTK in Circulating T cells of Non-Proliferative Diabetic Retinopathy Patients

Abstract Objective To explore the differential gene expression in peripheral blood immune cells of individuals with type 2 diabetes mellitus (DM), comparing those with and without non-proliferative diabetic retinopathy (NPDR).Methods From 117 potential participants, 51 were selected for detailed analysis: 9 healthy donors (HDs), 19 with DM, and 23 with NPDR. We analyzed peripheral blood mononuclear cells (PBMCs) using RNA sequencing and qPCR to identify differentially expressed genes (DEGs) and used flow cytometry to assess protein expression.Results In NPDR patients compared to those with DM alone, MerTK—a gene linked to inherited retinal dystrophies—was notably downregulated in PBMCs. Flow cytometry revealed MerTK predominantly in monocytes and myeloid-derived suppressor cells (MDSCs), with reduced expression in CD4 + and CD8 + T cells and natural killer T (NKT) cells. DM patients showed significant deviations in PBMC composition, especially in B cells, CD4 + T cells, and NK cells, compared to HDs.Conclusions The study indicates that MerTK expression in T cells within PBMCs could act as a viable blood biomarker for NPDR risk in DM patients. Furthermore, the regulation of T cells by MerTK might represent a critical pathway through which DM evolves into NPDR.