The prolonged calcium influx resulting from blue light exposure increases levels of reactive oxygen species in the eye including hydrogen peroxide and lipid peroxidation. Persistent production of metarhodopsin in the presence of blue light leads to its endocytosis and prolonged calcium influx, both of which can induce cell death. In flies, metarhodopsin can be converted back to Rh1 by orange light (λ = 580 nm). Upon blue illumination, Rh1 is activated to metarhodopsin initiating the phototransduction cascade. Blue light (λ = 480 nm) activates the G-protein coupled receptor Rhodopsin 1 (Rh1) within the rhabdomere, the light sensing organelle, of R1–R6 photoreceptors. In Drosophila, as in other organisms, blue light wavelengths induce retinal degeneration. However, the neuroprotective mechanisms utilized by photoreceptors to withstand the oxidative stress generated as a normal part of light exposure are not fully understood. Cells possess endogenous protective mechanisms to withstand lipid peroxidation and maintain redox homeostasis including gene regulatory mechanisms. Lipid peroxidation, once initiated, induces a cycle of oxidative damage that harms cellular membranes and eventually culminates in cell death. In particular, lipid peroxidation, the oxidation of membrane lipids, is an emerging hallmark of both neurodegenerative and age-associated ocular disease. The specialized nature and composition of photoreceptor neurons may increase their sensitivity to oxidative damage due to the energy demands of vision, the high concentration of peroxidation-sensitive polyunsaturated fatty acids, and exposure to light. Oxidative stress has been linked to the onset of human retinal degeneration. Light itself, although essential for vision, poses a stress to the visual system through photogeneration of reactive oxygen species. Together, these data provide insight into the neuroprotective gene regulatory mechanisms that enable photoreceptors to withstand light-induced oxidative stress. Developmental transitions during the first week of adult Drosophila life lead to an altered gene expression program in photoreceptors that includes reduced expression of genes that maintain redox and calcium homeostasis, reducing the capacity of six-day-old flies to cope with longer periods (8 h) of light exposure. Thus, six-day-old flies can withstand up to 3 h blue light exposure without undergoing retinal degeneration. Together, this gene expression program both counteracts the calcium influx resulting from prolonged light exposure, and ameliorates the oxidative stress resulting from this calcium influx. Our data demonstrate that under phototoxic conditions, Drosophila photoreceptors upregulate stress response pathways and simultaneously, downregulate expression of phototransduction components, ion transporters, and calcium channels.
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