Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid

Abstract

Aim The aim of this study is to assess the effectiveness of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDI) with a broad spectrum epigenetic activity, in improving filtration bleb survival as an adjunct therapy to glaucoma filtration surgery (GFS) in the rabbit model. Materials and methods Eighteen New Zealand White rabbits underwent GFS in the left eye and were randomized to receive either a subconjunctival (SC) injection of 0.1 mL SAHA (9.25 μg/mL) or balanced saline solution (BSS) at the end of surgery, or a 3-minute intraoperative topical application of 0.4 mg/mL mitomycin-C (MMC). Bleb survival and histology were compared. Results Blebs of rabbits receiving injections of SAHA survived an average (mean ± SD) of 23.2 ± 2.7 days. SAHA rabbits showed a nonsignificant improvement over rabbits that received an injection of BSS, which had a mean survival time of 19.7 ± 2.7 days ( p = 0.38) according to a one-way analysis of variance (ANOVA). Eyes receiving intraoperative topical MMC survived an average of 32.5 ± 3.3 days, which is significantly longer than both the control group treated with BSS ( p = 0.01) and the experimental group treated with the SAHA ( p = 0.0495). SAHA was well tolerated and showed no significant avascularity, necrosis, or conjunctival thinning. Conclusion Although it was well tolerated, a single intraoperative injection of SAHA did not significantly prolong bleb survival in the rabbit model. Clinical significance Epigenetic adjuncts hold promise for improving GFS outcome; however, future studies must continue to examine different administration protocols and dosages to substantiate their efficacy. How to cite this article Rodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37–41.

Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells

“…Clinically effective dosage of MMC is 0.02–0.4 mg/ml (0.002–0.04%) used intraoperatively 64 , 65 . Subconjunctival injection of SAHA (9.25 μg/ml and 50 μM) were given in New Zealand white rabbits to improve bleb survival and prevent fibrosis in Glaucoma filteration surgery 66 , 67 . Topically 25–350μM of SAHA has been administered in New Zealand white rabbits and Sprague–Dawley rats respectively, to prevent corneal haze/scarring post PRK 20 , 26 , 68 .…”

Novel Therapies for the Prevention of Fibrosis in Glaucoma Filtration Surgery

“…Methods of gene therapy involve increasing expressions of inhibitory genes and proteins in the cell cycle. Human p53 is a tumor suppressor gene that plays a key role in arresting cell cycle progression to allow DNA repair or inducing apoptosis if the damage is too extensive [ 172 ]. Many studies have demonstrated p53 as an active player in human Tenon’s fibroblast migration and growth [ 102 , 103 ].…”