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Miscellaneous (23)

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Abstract #69255 Published in IGR 18-1

Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery

Sharma A; Anumanthan G; Reyes M; Chen H; Brubaker JW; Siddiqui S; Gupta S; Rieger FG; Mohan RR
Investigative Ophthalmology and Visual Science 2016; 57: 3381-3389

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PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Harry S. Truman Memorial Veterans' Hospital Columbia, Missouri, United States 2One-Health One-Medicine Ophthalmology and Vision Research Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States.

Full article

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Classification:

12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)

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