Rhodopsin-Dependent Models of Drosophila Photoreceptor Degeneration

Abstract

Many model systems have been exploited to examine the various mechanisms and molecular defects that can lead to retinal degeneration. While humans and mice are the two major vertebrate organisms for these analyses, the invertebrate Drosophila melanogaster provides a compelling alternative model system to study hereditary retinal degeneration. The invertebrate and vertebrate photoreceptor cells are dramatically different in both structure and organization, their visual transduction second messenger systems, and the direction of change in membrane polarity as a result of light excitation (1, 2). However, the processes that lead to retinal degeneration may be conserved between vertebrates and invertebrates. This is exemplified by mutations in analogous molecules, most notably both dominant and recessive rhodopsin mutations. Drosophila is ideal for a genetic analysis of retinal degeneration due to its small size, rapid life cycle and ease of mutant generation. Drosophila has provided a large number of mutants that undergo light-dependent, light-enhanced, and light-independent retinal degeneration (3). These mutants are defective in both expected and novel components that are required for visual transduction and photoreceptor cell structure. Because there has not been an exhaustive search for Drosophila retinal degeneration mutants, we expect that many mechanisms and molecular details remain to be identified. Recent results have provided a wealth of information and new ideas about photoreceptor cell structure and physiology.