Pericyte Chemomechanics and the Angiogenic Switch: Insights Into the Pathogenesis of Proliferative Diabetic Retinopathy?

Abstract

Effects from the diabetic microenvironment appear sustainable in cell culture: pericytes derived from diabetic donor eyes seemingly possess a "metabolic memory" in vitro, which may be linked to original donor health status. Diabetes- and pericyte-dependent effects on EC growth and angiogenesis may reflect alterations in bioactive lipid, angiocrine, and chemomechanical signaling. Altogether, our results suggest that diabetes alters pericyte contractile phenotype and cytoskeletal signaling, which ultimately may serve as a key, initiating event required for retinal endothelial reproliferation, angiogenic activation, and the pathological neovascularization accompanying proliferative diabetic retinopathy.

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

“…In addition to large Cx43‐positive puncta located on the astrocytes and strings located on the endothelial cells, we detected additional small punctate labeling. While the precise location is not clear, these smaller plaques could be GJ formations between pericytes and endothelial cells, similar to ones observed using electron microscopy (Carlson, ; Durham, Dulmovits, Cronk, Sheets, & Herman, ).…”

Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches

“…Pericyte abundance, function and recruitment are remarkably altered in diabetes, contributing to microvascular damage in the retina, the kidney and the heart [45]. In fact, an early histopathologic feature of diabetic microangiopathy is the selective degeneration of pericytes in capillary vessels [46]. In the retina of diabetic patients, pericytes regress due to accelerated apoptosis, thus contributing to increased vascular permeability and retinal edema [47].…”

Pericytes Directly Communicate with Emerging Endothelial Cells During Vasculogenesis

“…Four connexin protein isoforms-Connexin37 (Cx37), Cx40, Cx43, and Cx45predominate in GJ of mature vasculature (Figueroa and Duling, 2009). Of these, Cx43 is known to be involved in PC differentiation (Hirschi et al, 2003) and vessel maturation (Durham et al, 2015), and plays a key role during epicardial development (Francis et al, 2011;Rhee et al, 2009). During vascular development, mouse Cx43 and Cx45 modulate TGFβ signaling such that disruption of these connexins leads to vascular defects including aberrant mural cell investment (Hirschi et al, 2003;Kruger et al, 2000).…”