Intraocular Gene Transfer of Ciliary Neurotrophic Factor Prevents Death and Increases Responsiveness of Rod Photoreceptors in theretinal degeneration slowmouse
Open Access
- 15 November 1998
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 18 (22) , 9282-9293
- https://doi.org/10.1523/jneurosci.18-22-09282.1998
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.Keywords
This publication has 48 references indexed in Scilit:
- Adenovirus-Mediated Gene Transfer of Ciliary Neurotrophic Factor Can Prevent Photoreceptor Degeneration in the Retinal Degeneration (rd) MouseHuman Gene Therapy, 1997
- Mammalian retinal pigment epithelial cells in vitro respond to the neurokines ciliary neurotrophic factor and leukemia inhibitory factorBiochemistry and Cell Biology, 1997
- Mouse models of human disease. Part II: recent progress and future directions.Genes & Development, 1997
- Ciliary neurotrophic factor, unlike nerve growth factor, supports neurite outgrowth but not synapse formation by adultLymnaea neuronsJournal of Neurobiology, 1996
- FK506 Immunosuppression to Control the Immune Reactions Triggered by First-Generation Adenovirus-Mediated Gene TransferHuman Gene Therapy, 1995
- Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) miceNeuron, 1992
- Cloning of the CDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathiesNeuron, 1992
- Development and degeneration of retina in rds mutant mice: immunoassay of the rod visual pigment rhodopsinBiochimica et Biophysica Acta (BBA) - General Subjects, 1990
- Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant miceDevelopmental Biology, 1986
- Light‐induced binding of 48‐kDa protein to photoreceptor membranes is highly enhanced by phosphorylation of rhodopsinFEBS Letters, 1984