Acta Pharmacologica Sinica (2009) 30: 413-423; doi: 10.1038/aps.2009.23

Acta Pharmacologica Sinica (2009) 30: 413-423; doi: 10.1038/aps.2009.23

Original Article

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

Jian-gang YANG^1,*, Nai-xue SUN¹, Li-jun CUI², Xiao-hua WANG¹, Zhao-hui FENG¹

¹Department of Ophthalmology, Second Affiliated Hospital of Medical School, Xi-an Jiaotong University; ²Department of Ophthalmology, First Affiliated Hospital of Medical School, Xi-an Jiaotong University, Xi-an 710004, China

Aim: The aim of the study was to evaluate the outcome of adenovirus-mediated p27^KIP1 (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 (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^KIP1expression 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.

Conclusion: 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．

Keywords: adenovirus; p27^KIP1; proliferation; glaucoma; surgery

The authors thank Dr Yu-mei TIAN ( Research Center for Neuroscience, Xi-an Jiaotong University ) for technical support in this study.

* Correspondence to Dr Jian-gang YANG.
E-mail jgyang.xjtu@gmail.com
Received 2008-11-30 Accepted 2009-02-19

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