title: Expression of Bcl-2 protects against photoreceptor degeneration in retinal degeneration slow (rds) mice.
abstract: The retinal degeneration slow or rds gene encodes rds/peripherin, an integral membrane glycoprotein in the outer segments of rod and cone photoreceptors. Mice homozygous for a null mutation in rds fail to develop outer segments and undergo subsequent degeneration of photoreceptors by the apoptotic pathway. Mutations in the human RDS gene are responsible for several forms of inherited blindness including autosomal-dominant retinitis pigmentosa and macular degeneration. Here, we examined the effects of ectopic Bcl-2 expression in transgenic photoreceptors on the rate of retinal degeneration in rds mutant mice. We observed an approximately twofold preservation of photoreceptors compared with nontransgenic rds mutant mice at 3 months. Immunoblot analysis showed similar levels of Bcl-2 in 2-, 3-, and 4-week-old transgenic mice. Expression of Bcl-2 in the rds mouse did not lead to outer segment formation and did not induce cell death. These results suggest that Bcl-2 expression may be an effective therapeutic strategy in humans with mutations in RDS or other genes that affect the integrity of photoreceptor outer segments.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78284, USA. nir@uthscsa.edu
authors.forename: I
authors.initials: I
authors.lastname: Nir
authors.forename: W
authors.initials: W
authors.lastname: Kedzierski
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: G H
authors.initials: GH
authors.lastname: Travis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics*; D064531:Peripherins; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology* / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D019076:Transgenes / Q000502:physiology
chemical_list: D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D019253:Proto-Oncogene Proteins c-bcl-2; C578996:Prph2 protein, mouse