bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations.
Apoptosis of photoreceptors occurs infrequently in adult retina but can be triggered in inherited and environmentally induced retinal degenerations. The protooncogene bcl-2 is known to be a potent regulator of cell survival in neurons. We created lines of transgenic mice overexpressing bcl-2 to test for its ability to increase photoreceptor survival. Bcl-2 increased photoreceptor survival in mice with retinal degeneration caused by a defective opsin or cGMP phosphodiesterase. Overexpression of Bcl-2 in normal photoreceptors also decreased the damaging effects of constant light exposure. Apoptosis was induced in normal photoreceptors by very high levels of bcl-2. We conclude that bcl-2 is an important regulator of photoreceptor cell death in retinal degenerations.
Chen
J
J
Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Flannery
J G
JG
LaVail
M M
MM
Steinberg
R H
RH
Xu
J
J
Simon
M I
MI
D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002470:Cell Survival; D003433:Crosses, Genetic; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D017299:Rod Opsins / Q000096:biosynthesis* / Q000235:genetics
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017299:Rod Opsins; D019204:GTP-Binding Proteins