Osusky R, Jiang M, Büchi E R, Spee C, Ye J, Ryan S J
Department of Ophthalmology, University of Southern California School of Medicine, Los Angeles, USA.
Graefes Arch Clin Exp Ophthalmol. 1995 Apr;233(4):220-5. doi: 10.1007/BF00183595.
Intraocular transplantation of genetically modified cells that release a particular substance could have a major impact on the treatment of various ocular diseases. We studied the expression of the reporter gene beta-galactosidase (lacZ) in transplanted retinal pigment epithelial (RPE) cells in vivo.
RPE cells from pigmented rabbits were transduced with the beta-galactosidase gene in a retroviral vector. Cells were then assayed for gene expression and transplanted subretinally into the eyes of New Zealand White rabbits. RPE cells that were transduced with a similar vector without the beta-galactosidase gene were used as controls. Rabbits were killed on days 1, 7, and 21 and the eyes processed for transmission electron microscopy
Neomycin-resistant rabbit RPE cells that showed beta-galactosidase activity were generated within 2-5 weeks. After transplantation, viable RPE cells that expressed the transgene and that phagocytosed rod outer segments were observed on days 1, 7, and 21
The results show that generation of genetically modified RPE cells is feasible and that the transplanted cells remain viable and continue to express the transgene in the subretinal space of the host animal for at least 21 days. Transplantation of such genetically modified RPE cells could provide a new tool for studying retinal diseases and, potentially, for correcting metabolic abnormalities in retinal degenerations and dystrophies.
