High-fat diet-induces retinal degeneration in Drosophila melanogaster

Age related macular degeneration (AMD) is a leading cause of vision loss in elderly adults. Despite correlations between a Western diet (rich in processed meats, fried foods, dairy and refined grains), AMD, and other neurodegenerative diseases, the mechanisms remain largely unclear. In comparison with the well-characterized mechanisms of light-dependent retinal degeneration, we aim to identify a potential mechanism for diet-induced retinal degeneration in Drosophila melanogaster fed on a high-fat diet (HFD) or a high-sugar diet (HSD). Newly emerged wild type adult flies were placed on standard food (ND) or on standard food supplemented with 4.5% coconut oil (HFD). Each group was further subdivided for exposure to constant darkness, cyclic light, or constant moderate light for 7 days. Retinal degeneration was measured in one-micron retina sections and defined as the percent ommatidia with fewer than normal rhabdomeres. Wild type HFD flies in constant darkness show a significant increase in retinal degeneration compared to controls on a ND. Retinal degeneration in wild type HFD flies exposed to constant moderate light approached levels for ND control flies. Interestingly, HFD flies exposed to constant moderate light did not show an increase in retinal degeneration compared to controls on a ND. Wild type flies fed on a ND supplemented with 30% sucrose (HSD) showed similar increases in retinal degeneration as flies on a HFD. One common mechanism involved in light-dependent retinal degeneration is ER-stress and activation of the unfolded protein response (UPR), and it has been linked to several age-related neurodegenerative diseases. Western blots of flies expressing the xbp1-EGFP fusion protein (a marker for ER- stress) fed on ND or HFD in varying light conditions revealed similar levels of activation of the UPR in all experimental conditions regardless of diet or light. Our results suggest that a HFD or a HSD induces retinal degeneration in a light-independent mechanism. In future experiments, we aim to determine whether HFD or HSD causes retinal degeneration by effects on mitochondrial function or oxidative stress.