Retinal pericytes are contractile cells adjacent to and provide support for endothelial cells of capillaries, which are essential in the regulation of retinal vasculature in the eye. Early stages of diabetic retinopathy are characterized by the loss of retinal pericytes, which lead to the development of advanced-stage pathology including angiogenesis. Although much is known about the etiology of diabetic retinopathy, the apoptotic pathway that incites retinal pericyte loss remains unclear. Our preliminary studies reveal that monocyte-derived macrophages secrete TGFβ1, which induces the expression and secretion of a TGFβ1-Induced, pro-apoptotic BIGH3 protein (TGFβ –Induced Gene Human Clone 3) leading to apoptosis of endothelial cells and retinal pericytes. This cascade of events has been attributed to the primary cause of retinal pericyte apoptosis and diabetic retinopathy. Macrophage TGF-β1 and BIGH3 are prediabetic biomarkers, and potential therapeutic targets for intervention of diabetic retinopathy for diabetic individuals. In the present study, we hypothesize that a similar macrophage-TGFβ–BIGH3 pathway may induce apoptosis in retinal pericytes. We will investigate the interaction between endothelial cells and retinal pericytes, as well as macrophages’ role on retinal pericyte expression of BIGH3 in response to TGFβ, and retinal pericyte apoptosis. Furthermore, we will also study the association of BIGH3 with integrin, a trans-membrane signaling protein receptor and its role to mediate retinal pericyte apoptosis. This novel study focuses on macrophage-mediated molecular pathway to impact diabetic retinopathy and it will provide opportunities of therapeutic intervention of this ocular eye disorder. Student trainees will be involved in these research projects, providing valuable experience on biomedical research.