New strategies in canine corneal wound healing for the veterinary ophthalmic patient
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Canine corneal fibrosis is a significant clinical problem in veterinary ophthalmology. Corneal wound healing following injury or infection often results in corneal fibrosis. The transformation of quiescent keratocytes to corneal myofibroblasts has been identified as the primary event in corneal wound healing that is responsible for fibrosis. Transforming growth factor beta (TGFβ) is a cytokine that plays a critical role in facilitating the cellular turnover of keratocytes to corneal myofibroblasts. It has been shown that inhibition of corneal myofibroblast formation reduces corneal fibrosis. Therefore, utilizing pharmacologic agents or gene therapy to modulate TGFβ function may be a useful strategy to prevent the development of corneal fibrosis. The aims of the first study were (1) to determine the efficacy of adeno-associated vector serotype 5 (AAV5) for delivering gene therapy to canine corneal fibroblasts (CCFs) and myofibroblasts (CCMs) using enhanced green fluorescent protein (GFP) marker gene and (2) evaluate the cytotoxicity of AAV5 to CCFs and CCMs using an in vitro model. Study results supported the finding that tested AAV5 is an effective and safe vector for canine corneal gene therapy in this in vitro model. In vivo studies are warranted. Study aims of the second study were to evaluate the safety and efficacy of the FDA-approved drug vorinostat (suberoylanilide hydroxamic acid) in the treatment of canine corneal fibrosis using an in-vitro model. Study results showed that vorinostat safely and effectively inhibits TGFβ1-induced myofibroblast proliferation in the canine cornea in vitro.
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