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Patricia A D'Amore; Retinal pericytes in health and disease. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4732.
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Presentation Description :
Capillaries are a two-cell system consisting of endothelial cells (ECs) that line the vessel lumen and the pericytes, located on the abluminal side of the endothelium. The pericyte is surrounded by a basement membrane that is produced in conjunction with endothelium, but the pericytes and ECs make physical contacts through discontinuities in the matrix. Only relatively recently has the importance of the pericyte in vascular development and integrity been appreciated. The isolation and culture of pericytes and ECs, in combination with the use of the developing retinal vasculature as an in vivo model, have allowed significant insight into the nature and role of the heterotypic intercellular communications. Paracrine and juxtacrine interactions between the ECs and pericytes mediated by soluble factors such as VEGF, PDGF B, TGF-ß1, Ang1 and Ang 2 as well as Notch signaling and gap junctions control vessel assembly and stabilization. Consequently, the dropout of pericytes, a characteristic change in background diabetic retinopathy, has significant impact on microvascular structure and function. Loss of only 15% of pericytes in an experimental model of pericyte deletion is associated with the rapid development of microaneurysms, focal leakage and acellular capillaries. Genetic deletion or overexpression of the various signaling molecules has provided a deeper understanding into their respective contributions to microvessel assembly, maturation and function. A number of these factors have become therapeutic targets for the treatment of ocular pathologies, particularly wet AMD and diabetic macular edema. Most notably, blockade of PDGF B signaling using a variety of agents is intended to delay vessel maturation with the goal of increasing anti-VEGF efficacy. Similarly, clinical trials are underway to manipulate the Tie2/Ang pathway with the goal of altering vessel permeability.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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