Current Biology
Volume 20, Issue 2, 26 January 2010, Pages 93-102
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Article
Requirement for an Enzymatic Visual Cycle in Drosophila

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Summary

Background

The visual cycle is an enzymatic pathway employed in the vertebrate retina to regenerate the chromophore after its release from light-activated rhodopsin. However, a visual cycle is thought to be absent in invertebrates such as the fruit fly Drosophila melanogaster.

Results

We demonstrate that an enzymatic visual cycle exists in flies for chromophore regeneration and requires a retinol dehydrogenase, PDH, in retinal pigment cells. Absence of PDH resulted in progressive light-dependent loss of rhodopsin and retinal degeneration. These defects are suppressed by introduction of a mammalian dehydrogenase, RDH12, which is required in humans to prevent retinal degeneration. We demonstrate that a visual cycle is required in flies to sustain a visual response under nutrient deprivation conditions that preclude de novo production of the chromophore.

Conclusions

Our results demonstrate that an enzymatic visual cycle exists and is required in flies for maintaining rhodopsin levels. These findings establish Drosophila as an animal model for studying the visual cycle and retinal diseases associated with chromophore regeneration.

Highlights

► A visual cycle exists outside of mammalian photoreceptor cells ► The Drosophila visual cycle prevents loss of rhodopsin during nutrient deprivation ► Impairment of the fly visual cycle causes retinal degeneration ► A human counterpart substitutes for a key enzyme in the fly visual cycle

CELLBIO
SIGNALING
MOLNEURO

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3

These authors contributed equally to this work

4

Present address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA