Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

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

Publication ,  Journal Article
Ahadome, SD; Abraham, DJ; Rayapureddi, S; Saw, VP; Saban, DR; Calder, VL; Norman, JT; Ponticos, M; Daniels, JT; Dart, JK
Published in: JCI Insight
August 4, 2016

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

August 4, 2016

Volume

1

Issue

12

Start / End Page

e87001

Location

United States

Related Subject Headings

  • Tretinoin
  • Pemphigoid, Benign Mucous Membrane
  • Mucous Membrane
  • Middle Aged
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
  • Fibrosis
  • Fibroblasts
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ahadome, S. D., Abraham, D. J., Rayapureddi, S., Saw, V. P., Saban, D. R., Calder, V. L., … Dart, J. K. (2016). Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring. JCI Insight, 1(12), e87001. https://doi.org/10.1172/jci.insight.87001
Ahadome, Sarah D., David J. Abraham, Suryanarayana Rayapureddi, Valerie P. Saw, Daniel R. Saban, Virginia L. Calder, Jill T. Norman, Markella Ponticos, Julie T. Daniels, and John K. Dart. “Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring.JCI Insight 1, no. 12 (August 4, 2016): e87001. https://doi.org/10.1172/jci.insight.87001.
Ahadome SD, Abraham DJ, Rayapureddi S, Saw VP, Saban DR, Calder VL, et al. Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring. JCI Insight. 2016 Aug 4;1(12):e87001.
Ahadome, Sarah D., et al. “Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring.JCI Insight, vol. 1, no. 12, Aug. 2016, p. e87001. Pubmed, doi:10.1172/jci.insight.87001.
Ahadome SD, Abraham DJ, Rayapureddi S, Saw VP, Saban DR, Calder VL, Norman JT, Ponticos M, Daniels JT, Dart JK. Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring. JCI Insight. 2016 Aug 4;1(12):e87001.

Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

August 4, 2016

Volume

1

Issue

12

Start / End Page

e87001

Location

United States

Related Subject Headings

  • Tretinoin
  • Pemphigoid, Benign Mucous Membrane
  • Mucous Membrane
  • Middle Aged
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
  • Fibrosis
  • Fibroblasts