The role of microglia in the development of diabetic retinopathy

Abstract

Diabetic retinopathy is a vision-threatening disease and remains the most feared complication for those living with diabetes. Historically, the disease has been considered primarily vascular in nature, based on clinically detectable vascular pathology. Nonetheless, it is now recognized that the retina undergoes a variety of cellular changes from the early onset of diabetes. In fact, one of the earliest changes to occur is a loss in vasoregulation, yet our understanding of the underlying mechanisms is lacking. Microglia, the resident immune cells of the central nervous system, perform a range of physiological, non-inflammatory functions to maintain retinal homeostasis which includes surveying the microenvironment to constantly monitor tissue health, neuronal surveillance to maintain synaptic integrity and vasoregulation, a recently discovered role that these cells additionally perform. The role of microglia in the development of diabetic retinopathy is well-established, centered around their contribution to inflammation which remains an integral component in disease pathogenesis, particularly in later stages of disease. However, recent findings reveal that early in the development of diabetes the vasoregulatory function of microglia is dysfunctional, leading to early vascular compromise. This review summarizes recent work to highlight how microglia are affected by diabetes and the implications of these changes in the development of diabetic retinopathy from pre-clinical to advanced stages of disease.