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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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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.
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.
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.
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.
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