Co-Treatment of Suberoylanilide Hydroxamic Acid and Mitomycin-C Induces the Apoptosis of Rabbit Tenon's Capsule Fibroblast and Improves the Outcome of Glaucoma Filtration Surgery

Abstract

Purpose: This study was undertaken to develop a new treatment modality that would be able to minimize fibrosis and provide better outcome with glaucoma filtration surgery (GFS). Methods: We examined whether co-treatment with mitomycin-C (MMC) and histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) efficiently induces apoptosis on rabbit Tenon's capsule fibroblasts (TCF) in vitro. We further examined the effect of co-treatment with SAHA and MMC on the alteration of IOP and the bleb survival in rabbits following GFS. Results: Co-treatment of MMC and SAHA efficiently induces apoptosis in TCFs via the up-regulation of p53 and increased phosphorylation of p53 on serine 15 and 392. Also, co-treatment of SAHA and low-dose MMC decreases IOP, prolongs bleb survival, and induces apoptosis of cells under the bleb area following GFS. Conclusion: This study shows that a co-treatment of SAHA and MMC could improve the outcome of GFS.

KEYWORDS:

• apoptosis
• deacetylase inhibitor
• glaucoma filtration surgery
• histone SAHA
• mitomycin-C