From Pathobiology to the Targeting of Pericytes for the Treatment of Diabetic Retinopathy

Abstract

Pericytes, the mural cells that constitute the capillaries along with endothelial cells, have long been associated with the pathobiology of diabetic retinopathy; however, therapeutic implications of this association remain largely unexplored. Pericytes appear to be highly susceptible to the metabolic challenges associated with a diabetic environment and there is substantial evidence that their loss may contribute to microvascular instability leading to the formation of microaneurysms, microhemorrhages, acellular capillaries, and capillary non-perfusion. Since pericytes are strategically located at the interface between the vascular and neural components of the retina, they offer extraordinary opportunities for therapeutic interventions in diabetic retinopathy. Moreover, the availability of novel imaging methodologies now allows for the in vivo visualization of pericytes, enabling a new generation of clinical trials that use pericyte tracking as clinical endpoints. The recognition of multiple signaling mechanisms involved in pericyte development and survival should allow for a renewed interest in pericytes as a therapeutic target for diabetic retinopathy.

Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice

“…In normal retinal capillaries, proper pericyte coverage ensures endothelial cell survival and BRB integrity [35]. Hyperglycemia causes intramural pericyte apoptosis and basement membrane thickening, leading to BRB breakdown and enhanced permeability [3,4,5]. Unfortunately, the current study did not examine the pericyte degeneration in diabetic retina.…”

“…Hyperglycemia evokes intramural pericyte apoptosis and basement membrane thickening, ultimately causing the dysfunction of blood-retinal barrier (BRB) and makes retinal vessels leaky [3,4,5]. Diabetic macular edema and blurry vision occur when the damaged vessels leak blood, fluid exudates, and lipids into the macula and retina [6,7].…”

Vascular Complications of Diabetes

“…Pericytes wrap around the arteriolar and capillary endothelial cells and participate in maintenance of capillary tone, growth, and resistance to damage from oxidative stress. 13,14 The disease is then marked by basement membrane thickening, endothelial cell permeability, and the formation of microaneurysms. 15 Broadly, there are 2 types of retinopathy, nonproliferative (background) and proliferative.…”

Mouse embryonic fibroblasts exhibit extensive developmental and phenotypic diversity

“…Pericytes, cells that girdle the abluminal side of endothelial cells in the perivascular space, may be the most consequential cell type in the microvascular complications of diabetes (25,26). The potential of the cell population to differentiate into pericytes has been explored in a mouse cranial window model that permits study of the microvasculature and associated cell types in vivo by intravital microscopy (27).…”