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Aging photoreceptors: light, stress and transcription
Author(s) -
Weake Vikki M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.256.1
Subject(s) - biology , transcriptome , visual phototransduction , gene expression , microbiology and biotechnology , rna splicing , drosophila melanogaster , alternative splicing , epigenetics , genetics , retinal degeneration , gene , senescence , neuroscience , exon , retina , rna
Aging is associated with functional decline of neurons and increased incidence of both neurodegenerative and ocular disease. Photoreceptor neurons in Drosophila melanogaster provide a powerful model for studying the molecular changes involved in functional senescence of neurons since decreased visual behavior precedes retinal degeneration. Flies show decreased phototaxis by day 40 without any significant retinal degeneration. We have identified gene expression changes that correlate with this functional decline in visual behavior during aging. By profiling the nuclear transcriptome of genetically‐labeled photoreceptors over a 40 day time course, we identified increased expression of genes involved in stress and DNA damage response, and decreased expression of genes required for neuronal function. These age‐regulated genes share specific sequence motifs and genomic features suggesting that both transcription factors and epigenetic mechanisms contribute to these expression changes. In addition, we have identified age‐regulated splicing events in photoreceptors, and shown that these differentially spliced genes are enriched for visual function and phototransduction. Indeed, proper splicing is necessary for visual behavior in young flies because photoreceptor‐specific RNAi against multiple splicing factors reduces phototaxis. To identify the environmental factors that drive the age‐related changes in gene expression and splicing, we have developed a blue light stress model that induces oxidative stress and eventual retinal degeneration. Using this light stress model, we have shown that there is a strong correlation between the gene expression changes in photoreceptors that are induced by light and during aging. However, there are also some significant differences suggesting that there are other factors that are involved in the age‐related gene expression changes. Current research focuses on identifying the transcription factors and epigenetic regulators that contribute to age‐related changes in gene expression and visual behavior. Support or Funding Information The authors thank the Ralph W. and Grace M. Showalter Research Trust, National Institutes of Health R01EY024905 to VW, Purdue University Center for Cancer Research (American Cancer Society Institutional Research Grant, IRG #58‐006‐53; NIH P30 CA023168), and shared Instrumentation Grant, NCRR 1 S10 RR023734‐01A1 for funding to support this work. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .