title: Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse.
abstract: 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.
authors.affiliation: Laboratoire de Transfert de Gènes, Centre de Recherche Université Laval Robert-Giffard, Beauport, Québec, Canada, G1J 2G3.
authors.forename: M
authors.initials: M
authors.lastname: Cayouette
authors.forename: D
authors.initials: D
authors.lastname: Behn
authors.forename: M
authors.initials: M
authors.lastname: Sendtner
authors.forename: P
authors.initials: P
authors.lastname: Lachapelle
authors.forename: C
authors.initials: C
authors.lastname: Gravel
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020934:Ciliary Neurotrophic Factor; D004195:Disease Models, Animal; D004596:Electroretinography; D018014:Gene Transfer Techniques; D006720:Homozygote; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D012243:Rhodopsin / Q000502:physiology
chemical_list: D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012243:Rhodopsin