Background: Light exposure induces oxidative stress, which contributes to ocular diseases of aging. Blue light provides a model for light‑induced oxidative stress, lipid peroxidation and retinal degeneration in Drosophila melanogaster. In contrast to mature adults, which undergo retinal degeneration when exposed to prolonged blue light, newly‑eclosed fies are resistant to blue light‑induced retinal degeneration. Here, we sought to characterize the gene expression programs induced by blue light in fies of diferent ages to identify neuroprotective pathways utilized by photoreceptors to cope with light‑induced oxidative stress.
Results: To identify gene expression changes induced by blue light exposure, we profled the nuclear transcriptome of Drosophila photoreceptors from one‑ and six‑day‑old fies exposed to blue light and compared these with dark controls. Flies were exposed to 3 h blue light, which increases levels of reactive oxygen species but does not cause retinal degeneration. We identifed substantial gene expression changes in response to blue light only in six‑day‑old fies. In six‑day‑old fies, blue light induced a neuroprotective gene expression program that included upregulation of stress response pathways and downregulation of genes involved in light response, calcium infux and ion transport. An intact phototransduction pathway and calcium infux were required for upregulation, but not downregulation, of genes in response to blue light, suggesting that distinct pathways mediate the blue light‑associated transcriptional response.
Conclusion: 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. Together, this gene expression program both counteracts the calcium infux resulting from prolonged light exposure, and ameliorates the oxidative stress resulting from this calcium infux. Thus, six‑day‑old fies can withstand up to 3 h blue light exposure without undergoing retinal degeneration. Developmental transitions during the frst 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 fies to cope with longer periods (8 h) of light exposure. Together, these data provide insight into the neuroprotective gene regulatory mechanisms that enable photoreceptors to withstand light‑induced oxidative stress.
Drosophila, Blue light, Retinal degeneration, Transcriptome, Photoreceptor, RNA-seq
Date of this Version
Hall H, Ma J, Shekhar S, Leon-Salas WD, Weake VM. Blue light induces a neuroprotective gene expression program in Drosophila photoreceptors. BMC Neurosci. 2018 Jul 20;19(1):43. doi: 10.1186/s12868-018-0443-y