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Originally published In Press as doi:10.1167/iovs.08-2277 on October 24, 2008
 (Investigative Ophthalmology and Visual Science. 2009;50:634-643.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2277
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Optical Effects of Anti-TGFβ Treatment after Photorefractive Keratectomy in a Cat Model

Jens Bühren,1 Lana Nagy,1,2 Jennifer N. Swanton,1 Shawn Kenner,1,3 Scott MacRae,1,2 Richard P. Phipps,1,4 and Krystel R. Huxlin1,2

1From the University of Rochester Eye Institute, the 2Center for Visual Science, the 3Institute for Optics, and the 4Department of Environmental Medicine, University of Rochester, Rochester, New York.

PURPOSE. To assess the contribution of corneal myofibroblasts to optical changes induced by photorefractive keratectomy (PRK) in a cat model.

METHODS. The transforming growth factor (TGF)-β-dependence of feline corneal keratocyte differentiation into {alpha}-smooth muscle actin ({alpha}SMA)-positive myofibroblasts was first tested in vitro. Twenty-nine eyes of 16 cats were then treated with –10 D PRK in vivo and divided into two postoperative treatment groups that received either 100 µg anti-TGFβ antibody for 7 days, followed by 50 µg dexamethasone for another 7 days to inhibit myofibroblast differentiation, or vehicle solution for 14 days (control eyes). Corneal thickness and reflectivity were measured by optical coherence tomography. Wavefront sensing was performed in the awake-behaving state before surgery and 2, 4, 8, and 12 weeks after surgery. Wound healing was monitored using in vivo confocal imaging and postmortem {alpha}SMA immunohistochemistry.

RESULTS. In culture, TGFβ caused cat corneal keratocytes to differentiate into {alpha}SMA-positive myofibroblasts, an effect that was blocked by coincubation with anti-TGFβ antibody. In vivo, anti-TGFβ treatment after PRK resulted in less {alpha}SMA immunoreactivity in the subablation stroma, lower corneal reflectivity, less stromal regrowth, and lower nonspherical higher order aberration induction than in control eyes. However, there were no intergroup differences in epithelial regeneration or lower order aberration changes.

CONCLUSIONS. Anti-TGFβ treatment reduced feline corneal myofibroblast differentiation in vitro and after PRK. It also decreased corneal haze and fine-grained irregularities in ocular wavefront after PRK, suggesting that attenuation of the differentiation of keratocytes into myofibroblast can significantly enhance optical quality after refractive surface ablations.






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