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

Published online

Journal Article

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease (AED), used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential and readily translatable antifibrotic therapy.

Full Text

Duke Authors

Cited Authors

  • Ahadome, SD; Abraham, DJ; Rayapureddi, S; Saw, VP; Saban, DR; Calder, VL; Norman, JT; Ponticos, M; Daniels, JT; Dart, JK

Published Date

  • August 4, 2016

Published In

Volume / Issue

  • 1 / 12

Start / End Page

  • e87001 -

PubMed ID

  • 27699226

Pubmed Central ID

  • 27699226

International Standard Serial Number (ISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.87001

Language

  • eng

Conference Location

  • United States