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Ajay Sharma, Jacob Brubaker, Marcos Reyes, Jason Rodier, Ashish Tandon, Rajiv Mohan; Attenuation of Glaucoma Filtration Surgery-induced Scarring by an FDA-approved Histone Deacetylase Inhibitor, Suberoylanilide Hydroxamic Acid (SAHA). Invest. Ophthalmol. Vis. Sci. 2013;54(15):4481.
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Glaucoma filtration surgery (GFS) is frequently used to treat glaucoma. Postoperative scar due to excessive wound healing is a major complication resulting in the failure of treatment. We found SAHA highly potent to inhibit corneal scarring in vivo without toxicity. This study tested the hypothesis that topical SAHA application following GFS is effective and safe to treat postoperative GFS-induced scarring.
Twelve New Zealand White rabbits underwent GFS to create a conjunctival flap using a beaver blade and a sclerotomy was performed. Animals received single intraoperative application of sponge soaked SAHA or balanced saline solution (BSS). The intraocular pressure (IOP) was measured using applanation tonometer with the animals under topical anesthesia. Clinical examination was performed to evaluate the general appearance, bleb score (1-4) and any toxicity of the treated eyes. On postoperative day 14, rabbits were sacrificed and the eyes were enucleated together with the conjunctiva to preserve the bleb and snap frozen in optimal cutting temperature (OCT) fluid. The tissues were sectioned and stained with hematoxylin and eosin (H&E), for α-smooth muscle actin (SMA), a myofibroblast marker and F actin, a marker for activated fibroblasts.
Intraoperative topical SAHA treatment showed notably less fibrosis in ocular tissue compared to the untreated control (up to 60%). An increased mean bleb score and normal intraocular pressure were observed in rabbits that received SAHA treatment indicating successfully functioning filtering bleb. H&E histology data revealed an overall decrease in the area of fibrotic deposit. Detection of larger blebs with aqueous pores and less fibrosis at the scleral flap demonstrated SAHA’s effective anti-fibrotic response. Immunostaining detected a decrease in SMA+ and F-actin+ cells (quantification and statistical analyses are underway). There were no apparent clinical signs of toxicity in the eyes of SAHA treated rabbits.
The intraoperative topical SAHA application significantly decreases postoperative fibrosis and improves the outcome of GFS. Larger animal study is warranted.
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