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 posterior capsule opacification (PCO). Hyperplasia of the lens epithelium is one of the main cellular events following phacoemulsification, and has been found to be an important feature contributing to opacification of the posterior capsule. Adenoviral vector-mediated transfer is a suitable method for transducing the herpes simplex virus thymidine kinase gene (HSV-tk) into proliferating cells, allowing for the selective killing of these cells by ganciclovir (GCV) treatment. To determine the potential of gene transduction for lens epithelial cells, we studied the transduction of rabbit lens epithelial cells with adenoviral vectors containing either the Escherichia coli beta-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 lens epithelial cells was at least 95% both in vitro and in vivo. In vivo transduction with HSV-tk adenoviral vector followed by GCV treatment significantly inhibited the development of PCO (p<0.001). These results suggest that adenoviral vector-mediated transfer of HSV-tk into the proliferating lens epithelial cells is feasible and may provide a novel therapeutic strategy for PCO.
Malecaze
F
F
CJF INSERM 9510, CHU Purpan, Toulouse, France. malecaze.fr@chu-toulouse.fe
Couderc
B
B
de Neuville
S
S
Serres
B
B
Mallet
J
J
Douin-Echinard
V
V
Manenti
S
S
Revah
F
F
Darbon
J M
JM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002386:Cataract / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004847:Epithelial Cells / Q000378:metabolism; D005240:Feasibility Studies; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006965:Hyperplasia; D066298:In Vitro Techniques; D007903:Lens Capsule, Crystalline / Q000473:pathology*; D008858:Microscopy, Phase-Contrast; D018918:Phacoemulsification / Q000009:adverse effects*; D011817:Rabbits; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir