Modulating ocular scarring in glaucoma filtration surgery using the epigenetic adjunct suberoylanilide hydroxamic acid

Cooper D. Rodgers, Zachary L. Lukowski, Jeff Min, Gina M. Martorana, Mary Kate Wilson, Jamie L. Schaefer, Monica A. Levin, Craig A. Meyers, C. Richard Blake, Gregory S. Schultz, Mark B. Sherwood

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)37-41
Number of pages5
JournalJournal of Current Glaucoma Practice
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Epigenetics
  • Glaucoma
  • Glaucoma filtration surgery
  • SAHA
  • Suberoylanilide hydroxamic acid
  • Trabeculectomy
  • Vorinostat

ASJC Scopus subject areas

  • Ophthalmology

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  • Cite this

    Rodgers, C. D., Lukowski, Z. L., Min, J., Martorana, G. M., Wilson, M. K., Schaefer, J. L., Levin, M. A., Meyers, C. A., Richard Blake, C., Schultz, G. S., & Sherwood, M. B. (2019). Modulating ocular scarring in glaucoma filtration surgery using the epigenetic adjunct suberoylanilide hydroxamic acid. Journal of Current Glaucoma Practice, 13(1), 37-41. https://doi.org/10.5005/jp-journals-10078-1246