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Vitamin A metabolism is linked to eye tissue fibrosis and scarring

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Mucous membrane pemphigoid is an autoimmune disease that causes inflammation and scarring in mucosal tissues. Affected individuals frequently exhibit scarring in the eye, which can lead to blindness in as many as 20% of patients. In this issue of JCI Insight, two related studies report on the underlying cause of fibrosis in the eye and implicate an important role for vitamin A metabolism. A group of researchers led by John Dart at UCLA show that the enzyme aldehyde dehydrogenase (ALDH), which produces the vitamin A metabolite retinoic acid, is elevated in mucous membrane tissue in the eye from mucous membrane pemphigoid patients. In mice, they demonstrate that an inhibitor of ALDH known as disulfiram can prevent inflammation in ocular mucosal tissue and decrease markers of fibrosis. A companion paper headed by Daniel Saban at Duke University explores the mechanism that contributes to eye fibrosis and uncovers a direct role for dendritic cells of the innate immune system. This study shows in a mouse model of eye fibrosis that dendritic cells produce high levels of aldehyde dehydrogenase. The resulting increase in retinoic acid triggers signaling in nearby fibroblasts that promotes fibrosis. Cumulatively, these two studies highlight a key role for retinoic acid in ocular fibrosis and suggest that inhibition of aldehyde dehydrogenase might potentially be used to prevent scarring in the eye.

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TITLE: Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

AUTHOR CONTACT: John Dart
University College London
Email: [email protected]

View this article at: http://insight.jci.org/articles/view/87001?key=8a651b204e228f66cb72

ACCOMPANYING ARTICLE

TITLE: Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

AUTHOR CONTACT: Daniel Saban
Duke University School of Medicine
Email: [email protected]

View this article at: http://insight.jci.org/articles/view/87012?key=5af8c5a9762ed12a91e2

JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to http://www.insight.jci.org.

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Corinne Williams
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