Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein ( fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance.
Normal vision requires precise regulation of the visual response. The deregulation of the visual response can lead to retinal diseases and blindness. The most frequent retinal disease is retinitis pigmentosa, and in 30%–40% of such cases rhodopsin, the light-sensitive protein, is mutated. Approximately 100 rhodopsin mutations have been identified; they affect folding, trafficking, and activity of the rhodopsin protein and induce consequent photoreceptor neuron death. Despite extensive studies, many aspects of retinal degeneration remain unclear. Drosophila is a suitable model organism to study retinal diseases. To understand the mechanisms of retinal degeneration, we studied the previously uncharacterized fatty acid transport protein ( fatp) gene in Drosophila. We found that flies that lack the fatp gene exhibit a deregulation of the visual response and an adult-onset and progressive retinal degeneration. In addition, we show that such retinal degeneration is due to the death of photoreceptor neurons in which rhodopsin proteins accumulate. In summary, we report a novel fly model of adult-onset retinal degeneration. We uncovered a novel and interesting mechanism by which Fatp, a potential regulator of lipid transport and metabolism, is responsible for the regulation of rhodopsin levels in the photoreceptor neurons.