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The Journal of Neuroscience, November 15, 1998, 18(22):9282-9293
Intraocular Gene Transfer of Ciliary Neurotrophic Factor Prevents Death and Increases Responsiveness of Rod Photoreceptors in the retinal degeneration slow mouse
Michel Cayouette1, Darren Behn2, Michael Sendtner3, Pierre Lachapelle2, and Claude Gravel1, 4 1 Laboratoire de Transfert de Gènes, Centre de Recherche Université Laval Robert-Giffard, Beauport, Québec, Canada, G1J 2G3, 2 Departments of Neurology/Neurosurgery and Ophthalmology, McGill University, Montreal Children's Hospital, Montreal, Canada, H3H 1P3, 3 Klinische Forschergruppe Neuroregeneration, Neurologische Universitäts-Klinik, Julius-Maximilians-Universität, 97080, Würzburg, Germany, and 4 Département de Psychiatrie, Faculté de Médecine, Université Laval, Cité Universitaire, Québec, Canada, G1K 7P4
Several mutations causing both photoreceptor degeneration and malfunction have been identified in humans and animals. Although intraocular injection of trophic factors has been shown to reduce photoreceptor death in a few conditions of rapid photoreceptor loss, it is unclear whether long-term beneficial changes in functional properties of affected photoreceptors can be obtained by treatment with these factors. The rds/rds mouse is a spontaneous mutant bearing a null mutation in the rds/peripherin gene, which is linked to many forms of dominant retinal degenerations in humans. Here, we report that intraocular adenovirus-mediated gene transfer of ciliary neurotrophic factor (CNTF) in this mutant reduces photoreceptor loss, causes a significant increase in the length of photoreceptor segments, and results in a redistribution and an increase in the retinal content of the photopigment rhodopsin. These effects are accompanied by a significant increase in the amplitude of the a- and b-waves of the scotopic electroretinogram. These results suggest that continuous administration of CNTF could potentially be useful for the treatment of some forms of retinal degeneration.
Key words: retina; ciliary neurotrophic factor; apoptosis; retinitis pigmentosa; gene transfer; photoreceptors; rhodopsin; electroretinogram
Copyright © 1998 Society for Neuroscience 0270-6474/98/18229282-12$05.00/0
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