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Editors Selection IGR 9-1

Basic research: ET-1 and ECM production in the lamina cribrosa

Comment by George Cioffi on:

21351 Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa, Rao VR; Krishnamoorthy RR; Yorio T, Experimental Eye Research, 2008; 86: 886-894

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ET-1 belongs to a family of vaso-active peptides and is known as an extremely potent vasoconstrictor in both the retina and optic nerve vasculature. More recently, additional effects of ET-1 have been described including pro-fibrotic effects, alterations of collagen synthesis, and direct effects on cell populations such as fibroblasts. The present study examines the role of ET-1 in the regulation of extracellular matrix (ECM) collagens within the optic nerve, using cultures of human lamina cribrosa cells. Rao et al. (528) hypothesize that ET-1 may act via direct effects on ECM production within the lamina cribrosa, resulting in pathophysiologic alterations. As elevated ET-1 has been found in some patients with glaucoma, ET-1 alterations of the laminar integrity could result in optic nerve susceptibility. The study shows that collagen types I, VI and total collagens are increased by ET-1 exposure to the laminar cells, and the increase is dose dependent. They conclude that these results suggest that ET-1 regulates ECM collagen synthesis in lamina cribrosa cells and may contribute to ECM remodeling at the level of lamina cribrosa of glaucoma patients who have elevated plasma and aqueous humor levels of endothelin-1. While the leap from cell culture to the clinic is extremely large, the hypothesis and findings are attractive and deserve further investigation.

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