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Vikki Weake; Age-related transcription changes in photoreceptor neurons are light-dependent. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3560.
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© ARVO (1962-2015); The Authors (2016-present)
Epigenetic mechanisms have been proposed to play key roles in the pathogenesis of ocular diseases associated with aging, such as diabetic retinopathy and age-related macular degeneration.An unanswered question is whether age-related changes in chromatin and gene expression drive the transition from aging to early disease state in ocular diseases of aging. Long-lived photoreceptor neurons might be uniquely vulnerable to the effects of aging because they must maintain the expression of genes important for the survival as well as cellular function throughout the adult lifespan. To characterize the mechanisms involved in age-dependent changes in gene expression, we sought to first characterize the transcriptome of aging photoreceptor neurons in Drosophila.
To identify genes that change expression profiles upon aging, we labeled and isolated nuclei from adult photoreceptor neurons and examined the transcriptome using RNA-seq at five time-points between 10 and 40 days post-eclosion.
Using this approach, we identified 1200 genes with age-dependent changes in expression profiles. Genes that are upregulated with age are functionally-enriched for GO terms involved in stress-response and protein synthesis, whereas genes that are downregulated with age are enriched for GO terms such as ion transport, cell adhesion and neuronal function. Strikingly, the downregulated genes show maximal expression changes at the earliest time points examined, while the upregulated genes change later in life.
This suggests that defects in transcription activation precede and may contribute to the increased stress response and cellular dysfunction in aging photoreceptor neurons. Since light is known to lead to increased oxidative stress in the eye, we tested the contribution of light to the age-dependent changes in gene expression. Notably, exposure of young flies to blue light induces similar changes in gene expression in photoreceptors to those that occur during aging, consistent with the hypothesis that the age-related changes in photoreceptor gene expression are dependent on light. Thus, blue light provides us with an experimental system to identify the epigenetic mechanisms involved in the transcriptional decline observed during photoreceptor aging.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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