The effect of halofuginone and pirfenidone on wound healing in experimental glaucoma filtration surgery

Abstract

Purpose. - To investigate the effects of halofuginone and pirfenidone on wound healing in experimental glaucoma filtration surgery (GFS). Study Design. - Animal experimentation. Methods. - A total of 42 male New Zealand albino rabbits were separated into 6 equal groups. A limbal-based trabeculectomy was performed on 5 groups, and Group I (control group) underwent no surgery and received no postoperative medication. For Group II (sham group), 1 drop 0.9% NaCl was instilled qid for 14 days. For Group III, 1% topical corticosteroid (prednisolone acetate) was instilled 1 drop qid for 14 days. For Group IV, 0.4 mg/mL mitomycin-C (MMC) was applied intraoperatively to the region of the scleral flap. For Group V, 0.5% pirfenidone was instilled 1 drop qid for 14 days postoperatively. For Group VI, a sponge soaked in 10 ng/mL halofuginone was applied to the surgical region for 3 mins. In addition, 1% topical corticosteroid was instilled x 1 drop qid for 14 days postoperatively for Groups IV, V and VI. After 14 days, sections prepared from the bleb regions of the enucleated eyes were evaluated histopathologically and immunohistochemically. Statistical analyses of the study were performed with Kruskal-Wallis variance analysis and the Mann-Whitney U test. Results. - With regard to fibroblasts, suppression of the number of mononuclear cells and immunohistochemical staining intensity of transforming growth factor-b (TGF-beta), fibroblast growth factor-b (FGF-beta) and platelet derived growth factor (PDGF), the corticosteroid, MMC, pirfenidone and halofuginone groups were seen to exhibit more effect than the sham group( P < 0.05). Compared to the pirfenidone and fuginone groups, inhibition of fibroblast and monocyte proliferation was determined to be lower in the MMC group (P < 0.05). The intensity of TGF-beta and FGF-beta staining was seen to be lower in these two treatment groups than in the MMC group (P < 0.05). Conclusions. - Halofuginone and pirfenidone may be used as effective alternative agents in delaying wound healing in glaucoma filtration surgery. (C) 2021 Elsevier Masson SAS. All rights reserved.