Sivak, Jeremy, Cherry, Allison, Demirs, John, Cepeda, Rosemarie, Long, Debby, Anderson, Karen and Jaffee, Bruce (2011) PATHOLOGICAL ANGIOGENESIS IS COORDINATED BY REPAIR EPITHELIAL CELLS IN THE CORNEA DISTINCTLY FROM INTERACTIONS WITH INFLAMMATORY INFILTRATES. Pharmacologic uncoupling of angiogenesis and inflammation during initiation of pathological corneal neovascularization.

Abstract

Recent investigations have suggested that neovascularization in the cornea results when a careful balance of pro- and anti-angiogenic factors is disrupted. Although a number of key anti-angiogenic factors in the normal cornea have been identified, the signals inducing this pathological angiogenesis have remained unclear. We have explored this question using an injury-driven model of corneal inflammation and angiogenesis. Initial experiments showed that limbal epithelial stem cells are required to main the cornea’s angiogenic privilege. Subsequently, repair epithelial cells resurface the damaged area and increase production of vascular endothelial growth factor-A (VEGF). This signal can be completely blocked by administration of a small molecule VEGF receptor-2 (VEGFR-2) antagonist, with little effect on the inflammation. By comparison, the angiogstatic steroid, Dexamethasone, inhibits both inflammation and angiogenesis, and targeted inhibition of the acute neutrophil response has no effect on neovascularization. These results provide evidence that corneal neovascularization and inflammation are distinct, but interrelated responses, and suggest a new model in which these processes are coordinated by signaling from repair epithelial cells.

Item Type:	Article
Keywords:	Angiogenesis, Cornea
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/4749