April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Differential Impact of PPARgamma Ligands and Anti-TGFß Treatment in an In Vivo Cat Model of Corneal Wound Healing
Author Affiliations & Notes
  • Krystel R. Huxlin
    Flaum Eye Institute,
    University of Rochester, Rochester, New York
  • Holly B. Hindman
    Flaum Eye Institute,
    University of Rochester, Rochester, New York
  • Scott MacRae
    Flaum Eye Institute,
    University of Rochester, Rochester, New York
  • Jens Buehren
    Dept of Ophthalmology, Goethe University Frankfurt, Frankfurt am Main, Germany
  • Patricia Sime
    Medicine (Pulmonary & Critical Care),
    University of Rochester, Rochester, New York
  • Richard Phipps
    Environmental Medicine,
    University of Rochester, Rochester, New York
  • Footnotes
    Commercial Relationships  Krystel R. Huxlin, None; Holly B. Hindman, None; Scott MacRae, None; Jens Buehren, None; Patricia Sime, None; Richard Phipps, None
  • Footnotes
    Support  NIH grants EY015836, EY017123, HL75432, K23 EY019353, Training Grant T32EY007125 and Core Grant P30EY0131, RPB
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2040. doi:
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      Krystel R. Huxlin, Holly B. Hindman, Scott MacRae, Jens Buehren, Patricia Sime, Richard Phipps; Differential Impact of PPARgamma Ligands and Anti-TGFß Treatment in an In Vivo Cat Model of Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2040.

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

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Abstract

Purpose: : Corneal scarring, a major cause of blindness worldwide, cannot yet be effectively controlled. Inhibition of the pro-fibrotic cytokine transforming growth factor ß (TGFß) only partially reduces myofibroblast differentiation, haze and the induction of higher order aberrations (HOAs). Here, we contrasted the effects of anti-TGFß antibodies with two peroxisome proliferator-activated receptor gamma (PPARgamma) ligands in a cat model of PRK-induced corneal wound healing.

Methods: : 27 adult, domestic, shorthair cats underwent bilateral -10D PRK followed by topical application of 10µM Troglitazone (Troglit, N=10 eyes), 10µM Rosiglitazone (Rosi, N=8 eyes), 50µg anti-TGFß antibody (Clone 1D11, N=10 eyes) or vehicle control (N=26 eyes) b.i.d. for 2 wks. Wavefront sensing was performed in the awake-fixating state pre-op, 2, 4, 8 and 12 wks post-op. OCT was used to measure changes in epithelial and stromal thickness, and backscatter reflectivity. Histology was performed 2 or 4 wks post-PRK (N=28 eyes) to assess relative expression of alpha smooth muscle actin (alpha SMA), a marker of differentiated myofibroblasts.

Results: : Rosi and Troglit inhibited alpha SMA expression more effectively than a-TGFß treatment (Rx). Though a-TGFß Rx inhibited stromal and epithelial regeneration, Rosi significantly increased epithelial regrowth, with central epithelium at 12 wks thicker by 17±7µm than in controls (a-TGFß Rx epithelia were 14±8µm thinner than controls 12 wks post-PRK). The stromas of Rosi, Troglit and control eyes regenerated to a thickness 51±12µm less than pre-op. Stromas treated with a-TGFß were 157±31µm thinner than pre-op. Finally, both PPARgamma ligands improved optical quality by decreasing haze and the induction of HOAs at a similar level to a-TGFß Rx.

Conclusions: : PPAR gamma ligands are just as effective at decreasing alpha SMA expression, haze and HOAs as a-TGFß Rx during corneal wound healing. However, they induced greater epithelial and stromal remodeling, suggesting different mechanisms of action and potential benefit for pathologically thin corneas.

Keywords: cornea: basic science • wound healing • optical properties 
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