Adenovirus-mediated suicide gene transduction: Feasibility in lens epithelium and in prevention of posterior capsule opacification in rabbits

The most common complication of cataract surgery is the development of post erior capsule opacification (PCO). Hyperplasia of the lens epithelium is on e of the main cellular events following phacoemulsification, and has been f ound to be an important feature contributing to opacification of the poster ior capsule. Adenoviral vector-mediated transfer is a suitable method for t ransducing the herpes simplex virus thymidine kinase gene (HSV-fk) into pro liferating cells, allowing for the selective killing of these cells by ganc iclovir (GCV) treatment. To determine the potential of gene transduction fo r lens epithelial cells, we studied the transduction of rabbit lens epithel ial cells with adenoviral vectors containing either the Escherichia coil be ta-galactosidase (lacZ) gene or the HSV-tk gene in vitro and in vivo in an experimental model of PCO. The efficiency of lacZ gene transfer in rabbit l ens epithelial cells was at least 95% both in vitro and in vivo. In vivo tr ansduction with HSV-tk adenoviral vector followed by GCV treatment signific antly inhibited the development of PCO (p < 0.001). These results suggest t hat adenoviral vector-mediated transfer of HSV-tk into the proliferating le ns epithelial cells is feasible and may provide a novel therapeutic strateg y for PCO.