Chemically induced retinal degeneration in the rdgB (retinal degeneration B) mutant of Drosophila.
Chemicals which affect different steps of the phototransduction cascade were used to identify the site of action of the rdgB gene product of Drosophila. In the rdgB mutant, the photoreceptor cells degenerate after several days of exposure to light, whereas raising the flies in the dark largely prevents the degeneration. In the rdgBKS222 mutant, which was used in the present studies, the light-induced degeneration is characterized by (1) selective degeneration of the peripheral but not the central photoreceptor cells; (2) random distribution of degenerated cells among ommatidia; and (3) the degeneration is specific to the rdgB but not the wild-type photoreceptor cells. In the present study, we show that application of specific chemical agents to the eyes of rdgBKS222 flies in the dark mimics the effects of light and causes retinal degeneration indistinguishable from light. The agents used in these studies are the metabolically stable GTP analogs GTP gamma S and Gpp(NH)p as well as fluoride ions, which are known to activate the transducing guanine nucleotide binding protein (G-protein of fly photoreceptors). It is unlikely that the chemically induced retinal degeneration is mediated by effects on energy metabolism, since application of the metabolic inhibitors CN- and 2-deoxy-D-glucose did not increase the extent of retinal degeneration over that observed in control flies treated with Ringer solution. The GDP analog GDP beta S, which inhibits G-protein activity, greatly reduced the extent of retinal degeneration in the dark, over that observed in control flies treated with Ringer solution. These results suggest that activation of the G-protein precedes the step in the transduction cascade that leads to retinal degeneration and provides a powerful tool to investigate the molecular mechanism of light-induced degeneration in the rdgB mutant.
Rubinstein
C T
CT
Department of Physiology, Hebrew University of Jerusalem, Israel.
Bar-Nachum
S
S
Selinger
Z
Z
Minke
B
B
D000818:Animals; D003624:Darkness; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000502:physiology; D004594:Electrophysiology; D005459:Fluorides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D009154:Mutation; D009410:Nerve Degeneration; D012160:Retina / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005459:Fluorides