Blue light induces a neuroprotective gene expression program in Drosophila photoreceptors.

Publisher: BioMed Central Country of Publication: England NLM ID: 100966986 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2202 (Electronic) Linking ISSN: 14712202 NLM ISO Abbreviation: BMC Neurosci Subsets: MEDLINE

Original Publication: London: BioMed Central, [2000-

Light*; Drosophila melanogaster/*metabolism ; Gene Expression Regulation/*physiology ; Photoreceptor Cells, Invertebrate/*metabolism; Animals ; Calcium Channels/metabolism ; Drosophila ; Gene Expression/physiology ; Neuroprotection/physiology ; Retinal Degeneration/metabolism

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 flies are resistant to blue light-induced retinal degeneration. Here, we sought to characterize the gene expression programs induced by blue light in flies of different 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 profiled the nuclear transcriptome of Drosophila photoreceptors from one- and six-day-old flies 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 identified substantial gene expression changes in response to blue light only in six-day-old flies. In six-day-old flies, blue light induced a neuroprotective gene expression program that included upregulation of stress response pathways and downregulation of genes involved in light response, calcium influx and ion transport. An intact phototransduction pathway and calcium influx 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 influx resulting from prolonged light exposure, and ameliorates the oxidative stress resulting from this calcium influx. Thus, six-day-old flies can withstand up to 3 h blue light exposure without undergoing retinal degeneration. 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. Together, these data provide insight into the neuroprotective gene regulatory mechanisms that enable photoreceptors to withstand light-induced oxidative stress.

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P30 CA023168 United States CA NCI NIH HHS; P40 OD018537 United States OD NIH HHS; R01 EY024905 United States EY NEI NIH HHS

Keywords: Blue light; Drosophila; Photoreceptor; RNA-seq; Retinal degeneration; Transcriptome

0 (Calcium Channels)

Date Created: 20180722 Date Completed: 20190507 Latest Revision: 20190507

20250114

PMC6053765

10.1186/s12868-018-0443-y

30029619