Adenovirus-Mediated Gene Therapy Using Human p21WAF-1/Cip-1to Prevent Wound Healing in a Rabbit Model of Glaucoma Filtration Surgery

Todd W. Perkins
2002 Archives of Ophthalmology  
Objective: To determine if adenovirus-mediated p21 WAF-1/Cip-1 (p21) gene therapy can prevent fibroproliferation and wound healing in a rabbit model of glaucoma filtration surgery. Methods: In vitro studies were performed using rabbit Tenon fibroblasts harvested from fresh tissue. In vivo studies were conducted in New Zealand white rabbits. A fullthickness sclerotomy was performed under a limbalbased conjunctival flap. Reagents tested included a replication-deficient recombinant adenovirus
more » ... ining the human p21 gene (rAd.p21); the nonspecific marker gene for green fluorescent protein or ␤-galactosidase; mitomycin, 0.5 mg/mL; and balanced saline solution. Each treatment was applied episclerally for 5 minutes before the sclerotomy using a soaked cellulose sponge placed under the surgically created conjunctival flap. Independent experiments were conducted to (1) monitor changes in intraocular pressure during a 30-day period after treatment and examine surgical site histological features, (2) examine changes in bleb morphologic features over 30 days, (3) determine outflow facility 14 days after treatment, and (4) examine the localization and persistence of rAd.p21 expression between 3 and 60 days after treatment. Results : Treatment of Tenon fibroblasts with rAd.p21 resulted in a dose-dependent inhibition of DNA synthe-(REPRINTED) ARCH OPHTHALMOL / VOL 120, JULY 2002 WWW.ARCHOPHTHALMOL.COM 941
doi:10.1001/archopht.120.7.941 pmid:12096965 fatcat:quyzoccqoffifetwazzdrh6wpq