Targeted RNAi screen identifies transcriptional mechanisms that prevent premature degeneration of adult photoreceptors.

Aging is associated with a decline in visual function and increased prevalence of ocular disease, correlating with changes in the transcriptome and epigenome of cells in the eye. Here, we sought to identify the transcriptional mechanisms that are necessary to maintain photoreceptor viability and function during aging. To do this, we performed a targeted photoreceptor-specific RNAi screen in to identify transcriptional regulators whose knockdown results in premature, age-dependent retinal degeneration.

Aging and Light Stress Result in Overlapping and Unique Gene Expression Changes in Photoreceptors.

Advanced age is one of the leading risk factors for vision loss and eye disease. Photoreceptors are the primary sensory neurons of the eye. The extended photoreceptor cell lifespan, in addition to its high metabolic needs due to phototransduction, makes it critical for these neurons to continually respond to the stresses associated with aging by mounting an appropriate gene expression response.

Proper control of R-loop homeostasis is required for maintenance of gene expression and neuronal function during aging.

Age-related loss of cellular function and increased cell death are characteristic hallmarks of aging. While defects in gene expression and RNA metabolism have been linked with age-associated human neuropathies, it is not clear how the changes that occur in aging neurons contribute to loss of gene expression homeostasis. R-loops are RNA-DNA hybrids that typically form co-transcriptionally via annealing of the nascent RNA to the template DNA strand, displacing the non-template DNA strand.

Characterizing a gene expression toolkit for eye- and photoreceptor-specific expression in Drosophila.

Binary expression systems are a powerful tool for tissue- and cell-specific research. Many of the currently available eye-specific drivers have not been systematically characterized for their expression level and cell-type specificity in the adult eye or during development. Here, we used a luciferase reporter to measure expression levels of different drivers in the adult eye, and characterized the cell type-specificity of each driver using a fluorescent reporter in live 10-day-old adult males.

Proper splicing contributes to visual function in the aging Drosophila eye.

Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age-related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expression in photoreceptors, including downregulation of genes encoding splicing factors. Here, we characterized the significance of these age-regulated splicing-associated genes in both splicing and visual function.

Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence.

Background: 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. Here, we sought to identify gene expression changes and the genomic features of differentially regulated genes in photoreceptors that contribute to visual senescence.