Adenovirus-mediated delivery of p27^KIP1 to prevent wound healing after experimental glaucoma filtration surgery

Aim： The aim of the study was to evaluate the outcome of adenovirus-mediated p27^KIP1 （Ad-p27） expression on wound heal- ing 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 （P〈0.01）, 14 （P〈0.01） and 21 （P〈0.05）. On d 28, IOP remained significantly decreased in the Ad-p27 group compared with the PBS group （P〈0.05）. 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 p27^KIP1 expression in conjunctival epithelium （P〈0.01）, relatively high expression in superficial scleral stroma （P〈0.01）, 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.