Diabetes associated pericyte metabolic signatures and pathogenesis of diabetic retinopathy

Pericytes are metabolically active perivascular supporting cells. They are essential for establishing and maintaining the inner blood retinal barrier and retinal neurovascular homeostasis. In diabetic retinopathy, the chronic hyperglycemic environment adversely affects pericyte functions including their glucose flux and metabolism. The early alterations in pericyte metabolic signatures during diabetes make them susceptible as an early damage target. Altered pericyte glucose flux through the polyol pathway, pentose phosphate pathway, hexosamine biosynthesis pathway, protein kinase C pathway, and advanced glycated end products pathway are responsible for mitochondrial dysfunction, inflammation, and oxidative stress. These metabolic changes in pericytes regulate vascular blood flow and tight junctions' integrity leading to vascular dysfunction and disease progression. This review aims to discuss the current understanding of pericyte metabolic signatures and altered glucose metabolism under hyperglycemic conditions like those present in diabetes. We also aim to highlight the need for further investigation of how pericyte metabolic activities, particularly among pericyte subtypes of the retina and other organs, are coordinated. This knowledge will help to further our understanding of how to preserve the blood tissue barrier and its function, and to prevent not only diabetic retinopathy but also vascular dysfunction in other organs impacted by diabetes.