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Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jacob W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan; Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2016;57(7):3381-3389. doi: 10.1167/iovs.15-18750.
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The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).
A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 μM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, α-smooth muscle actin (αSMA), and F-actin staining. Furthermore, SAHA-mediated acetylation of histones in corneal fibroblasts and conjunctiva were determined by Western blot analysis.
Suberoylanilide hydroxamic acid treatment after GFS showed no signs of edema, corneal opacity, endophthalmitis, or cataract formation. Morphometric analysis of SAHA-treated eyes showed higher bleb length (P < 0.001), bleb area (P < 0.05), lower IOP (P < 0.01), and decreased vascularity compared to control. Furthermore, SAHA treatment showed significantly reduced levels of αSMA (P < 0.001), F-actin (P < 0.01), and collagen deposition (P < 0.05) at the sclerotomy site. In addition, SAHA treatment increased the acetylation status of H3 and H4 histones in corneal fibroblasts and conjunctiva.
This study demonstrates that HDAC inhibition is an attractive pharmacologic target to modulate GFS wound healing, and SAHA, an HDACi, can be a useful adjunct to improve the GFS outcome.
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