Requirement for an Enzymatic Visual Cycle in Drosophila

Abstract

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. 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. 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.