Do photoreceptor cells cause the development of retinal vascular disease?

Abstract

The retinal vasculature is affected in a number of clinically important retinopathies, including diabetic retinopathy. There has been a considerable amount of research into the pathogenesis of retinal microvascular diseases, but the potential contribution of the most abundant cell population in the retina, photoreceptor cells, has been largely overlooked. This review summarizes ongoing research suggesting that photoreceptor cells play a critical role in the development of retinal vascular disease in diabetic retinopathy and other retinopathies.

Keywords: Microvasculature; Opsin; Photoreceptors; Retina.

Fig 1

Photomicrographs illustrating degeneration of the retinal vasculature in response to a molecular defect that occurs only in photoreceptor cells (P23H mutation of opsin). Diabetes likewise causes capillary degeneration in wildtype animals, but at a much slower pace. Samples collected at 10 months of age (8 months of diabetes). Representative degenerated retinal capillaries are identified by arrows.

Fig 2

Photoreceptor cells contribute to leukocyte-mediated killing of retinal endothelial cells. Leukocytes from wildtype (WT) mice diabetic for 8 months were co-cultured with mouse retinal endothelial cells. Leukocytes from WT diabetic mice caused more endothelial cell death than did leukocytes from WT nondiabetic animals. Leukocytes from opsin^−/− animals lacking photoreceptor cells who were likewise diabetic for the same duration were protected from the diabetes-induced increase in leukocyte-mediated cytotoxicity to retinal endothelial cells.Reprinted without change from Tonade, Liu; and Kern (2016) Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes, Invest Ophthalmol Vis Sci, .57, 4264-4271. Creative Commons Attribution (CC BY) license

Fig 3

Summary of postulated roles of photoreceptors in the development of dysfunctional and degenerating retinal capillaries.