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Blocking apoptosis prevents blindness in Drosophila retinal degeneration mutants

Abstract

Apoptosis is a gene-directed form of cell death that is essential for normal development and health. Yet abnormally high levels of apoptosis are linked to many degenerative diseases1. Some important biochemical events in apoptosis have been identified2, but the therapeutic utility of blocking cell death remains unclear. An important question in this regard is whether cells rescued from apoptosis can function. We have investigated the mechanism of cell death in two Drosophila mutant strains that exhibit age-related retinal degeneration. One of these mutations also occurs in humans, where it causes retinitis pigmentosa. We found that retinal cell death in rdgC and ninaERH27/+ flies occurred by apoptosis and was blocked by eye-specific expression of the baculoviral cell survival protein p35. Most importantly, the mutant flies expressing p35 showed significant retention of visual function. The results demonstrate a therapeutic benefit of late-stage inhibition of apoptosis to flies, and suggest that similar results may be obtained in higher organisms.

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Figure 1: Photoreceptor cells in light-reared ninaERH27/+ flies exhibit apoptotic morphology.
Figure 2: Retinal degeneration in ninaERH27/+ flies is rescued by p35 expression.
Figure 3: Retinal degeneration in rdgC306 flies is rescued by p35 expression.
Figure 4: Optomotor responses in ninaERH27/+ flies are rescued by p35 expression.
Figure 5: Electrophysiological responses in rdgC306 flies are rescued by p35 expression.

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Acknowledgements

We thank L. Smith and J. Hall for assistance and instruction in the measurement of optomotor responses and retinal ERGs; J. E. O'Tousa for rdgC and ninaERH27 mutant strains; and J. Hall and H. R. Horvitz for critical reading of the manuscript. F.F.D. was a postdoctoral associate and H.S. is an investigator with the Howard Hughes Medical Institute.

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Correspondence to Hermann Steller.

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Davidson, F., Steller, H. Blocking apoptosis prevents blindness in Drosophila retinal degeneration mutants. Nature 391, 587–591 (1998). https://doi.org/10.1038/35385

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