April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Pirfenidone potential for treating corneal fibrosis
Author Affiliations & Notes
  • Rajiv R Mohan
    Mason Eye Institute, University of Missouri-Columbia, Columbia, MO
    Ophthalomology Research, Harry S Truman VA Hospital, Columbia, MO
  • Ashish Tandon
    Mason Eye Institute, University of Missouri-Columbia, Columbia, MO
  • Michael K Fink
    Ophthalomology Research, Harry S Truman VA Hospital, Columbia, MO
    College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO
  • Ajay Sharma
    Mason Eye Institute, University of Missouri-Columbia, Columbia, MO
    Ophthalomology Research, Harry S Truman VA Hospital, Columbia, MO
  • Nishant R Sinha
    Mason Eye Institute, University of Missouri-Columbia, Columbia, MO
  • Prashant R Sinha
    Mason Eye Institute, University of Missouri-Columbia, Columbia, MO
    Ophthalomology Research, Harry S Truman VA Hospital, Columbia, MO
  • Jason T Rodier
    Mason Eye Institute, University of Missouri-Columbia, Columbia, MO
    Ophthalomology Research, Harry S Truman VA Hospital, Columbia, MO
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5146. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Rajiv R Mohan, Ashish Tandon, Michael K Fink, Ajay Sharma, Nishant R Sinha, Prashant R Sinha, Jason T Rodier; Pirfenidone potential for treating corneal fibrosis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5146.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: Pirfenidone is clinically approved in Europe and Asia for the treatment of idiopathic pulmonary fibrosis. Pirfenidone is shown to reduce the expression of several profibrogenic cytokines including TGFβ, CTGF etc. implicated in the pathogenesis of corneal fibrosis. We tested the effects of pirfenidone on human corneal fibroblast (HCF) viability, proliferation, migration, and death (apoptosis/necrosis), and corneal myofibroblast inhibition using an in vitro model.

Methods: Human donor corneas were used to generate HCF primary cultures. HCFs were exposed to TGFβ1 (5ng/ml) to produce myofibroblasts/fibrosis for 7-9 days under serum-free conditions. Cultures were treated with pirfenidone (0-300µg/ml) in +/- of TGFβ1 to study its effects on HCF function and myofibroblast inhibition. Real-time PCR, western blotting, immunofluorescence, TUNEL, scratch, trypan blue and MTT assays were used to study pirfenidone effects on HCF viability, migration, proliferation and differentiation to myofibroblasts.

Results: Pirfenidone 200µg/ml or less demonstrated no significant loss of HCF viability at 12h, 24h and 48h. Pirfenidone 200µg/ml showed remarkable decrease in HCF proliferation (7-22%), migration (47-73%), and differentiation (up to 93%) without significant toxicity/apoptosis. Further, this Pirfenidone dose significantly reduced myofibroblast formation measured by alpha smooth muscle actin mRNA (84-93%; p<0.001) and protein (68-76%; p<0.01) levels.

Conclusions: Pirfenidone has the potential to treat corneal scarring effectively without compromising normal HCF function. In vivo studies are warranted.

Keywords: 480 cornea: basic science • 484 cornea: stroma and keratocytes • 765 wound healing  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×