Role of the Polyol Pathway in High Glucose–Induced Apoptosis of Retinal Pericytes and Proliferation of Endothelial Cells

Abstract

ARI rescued pericytes from high glucose-induced apoptosis and maintained the levels of TGF-beta, resulting in the prevention of cocultured EC growth.

Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation

“…Sorbitol accumulation following polyol pathway activation reportedly promotes degeneration and apoptosis of several cell types in high glucose conditions (37). In our study, hyperglycemia promoted sorbitol accumulation followed by Schwann cell de-differentiation, which also occurs following peripheral nerve injury.…”

Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment

“…showing that pericytes are able to inhibit EC proliferation when co-cultured in direct contact [17,20]. However, those results were obtained with bovine or porcine cells, not human-derived cells.…”

“…Consequently, it is important to study their pathophysiological mechanisms in experimental contests where the interactions between these two cell types are preserved. Even though some studies in the literature used EC-pericyte co-cultures [16][17][18], in our knowledge this is the first time in which pericytes and EC of human origin have been utilized.…”

Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

“…43 The selective loss of pericytes has been reported to be the hallmark of DR 44,45 and pericyte loss in dogs has been linked to AR activity 17,46,47 ; however, the selective loss of pericytes versus endothelial cells is controversial. [48][49][50][51][52] Using rat retinal capillary pericyte (TR-rPCT) and endothelial (TR-iBRB) cells, we have previously reported that short-term hyperglycemia results in pericyte apoptosis that is linked to the AR-catalyzed accumulation of sorbitol and that pericytes exposed to hypoglycemia demonstrate ER stress-linked apoptotic signaling. 53 More recently, Leal et al have reported that long-term hyperglycemia induces apoptosis in retinal endothelial (TR-iBRB) cells independent of caspase activation.…”