Adenovirus-mediated delivery of p27KIP1 to prevent wound healing after experimental glaucoma filtration surgery

Abstract

Aim: The aim of the study was to evaluate the outcome of adenovirus-mediated p27KIP1 (Ad-p27) expression on wound healing after filtration surgery and to investigate the inhibition of cell proliferation induced by Ad-p27. Methods: We constructed the adenovirus recombinant vector Ad-p27 and administered it to a rabbit model of glaucoma filtration surgery by subconjunctival injection; phosphate-buffered saline (PBS) and mitomycin C (MMC) were used as controls. Intraocular pressure (IOP), bleb scores, and anterior chamber depths were observed during a 28-d period. Histological examinations, fluorescence observations and Western blot analyses were evaluated. Results: Ad-p27 enhanced the surgical outcome and inhibited cell proliferation when compared with PBS. Bleb scores in the Ad-p27-treated eyes were higher than those in the PBS-treated eyes on d 7 (P0.01), 14 (P0.01) and 21 (P0.05). On d 28, IOP remained significantly decreased in the Ad-p27 group compared with the PBS group (P0.05). However, no differences in bleb scores or IOPs were observed between the Ad-p27 and MMC groups. Histological analysis showed that total cell numbers were markedly reduced, and less scar tissue was observed at the surgical site in eyes treated with Ad-p27. The number of fibroblasts was decreased in Tenon's capsule in Ad-p27-treated eyes; however, a marked and diffuse signal from the green fluorescent protein (GFP) was observed in fibroblasts. Western blot analysis revealed a high level of p27KIP1 expression in conjunctival epithelium (P0.01), relatively high expression in superficial scleral stroma (P0.01), and low expression in corneal epithelium in the Ad-p27 group. Conclusions: Ad-p27 administration significantly improves the outcome of filtration surgery and inhibits postoperative proliferation in rabbit eyes. These findings suggest that p27 KIP1 is a potential adjunctive agent for inhibition of wound healing after filtration surgery. © 2009 CPS and SIMM.