Title:Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences
Volume: 20
Issue: 26
Author(s): Elena Beltramo and Massimo Porta
Affiliation:
Keywords:
Apoptosis, diabetic retinopathy, endothelial cells, extracellular matrix, pericytes, pericyte loss.
Abstract: The onset of diabetic retinopathy is characterized by morphologic alterations of the microvessels, with thickening
of the basement membrane, loss of inter-endothelial tight junctions and early and selective loss of pericytes, together
with increased vascular permeability, capillary occlusions, microaneurysms and, later, loss of endothelial cells (EC). A
key role in the evolution of the disease is played by pericytes, specialized contractile mesenchymal cells of mesodermal
origin, that, in capillaries, exert a function similar to smooth muscle cells in larger vessels, regulating vascular tone and
perfusion pressure. Thickening of the basement membrane, together with systemic and local hypertension, hyperglycaemia,
advanced glycation end-product formation and hypoxia, may disrupt the tight link between pericytes and EC causing
pericyte apoptosis, while endothelium, deprived of proliferation control, can give rise to new vessels. Pericyte dropout has
great consequences on capillary remodelling and may cause the first abnormalities of the diabetic eye which can be observed
clinically. Hyperglycaemia and local hypertension are known to be a direct cause of pericyte apoptosis and dropout,
and intracellular biochemical pathways of the glucose metabolites have been explored. However, the exact mechanisms
are not yet fully understood and need further clarification in order to develop new effective drugs for the prevention
of retinopathy.
