Transcriptional Changes in Aging Photoreceptor Cells of Drosophila melanogaster

Abstract

As the human population ages, there is an increased risk for ocular diseases such as age‐related macular degeneration (AMD), glaucoma, and diabetic retinopathy. Specifically, AMD is characterized by deterioration of the macula of the eye and is the leading cause of the loss of central vision in those individuals over 60. Twin studies have previously shown that non‐genetic, environmental factors contribute more than 50% of the overall risk for developing age‐related ocular diseases such as AMD. For this reason, epigenetic mechanisms have been thought to play a major role in the environmental‐based risks associated with AMD. The epigenetic factors that contribute to vision loss in the aging eye have yet to be identified, but are thought to play a pivotal role in maintaining proper ocular ability, as misregulation of these factors could lead to transcriptional changes in gene expression. We hypothesize that as photoreceptor cells age, there are changes in gene expression that contribute to the loss of vision seen later in life. Because age‐related changes in gene expression are cell autonomous, Drosophila melanogaster photoreceptor neurons were chosen as a model system due to the likelihood that these post‐mitotic cells are more sensitive to changes in gene expression. Photoreceptor cells are also likely to be at an increased vulnerability to the effects of aging because they must constantly express high levels of proteins involved in phototransduction in order to maintain their function throughout the adult lifespan. Using these Drosophila photoreceptors, we are conducting a study on the effects of aging on gene expression. Experiments to globally characterize the transcriptome of isolated nuclei from the R1‐R6 photoreceptor cells of male Drosophila were performed using RNA‐sequencing technology. We then used cluster analysis on this sequencing data to identify genes that exhibited statistically significant changes in gene expression at specific fly‐age time points. Using this cluster analysis data, we will prioritize genes from each cluster to generate subsets of genes to test through qRT‐PCR experiments on both dissected eye and isolated nuclear samples. This qRT‐PCR will allow us to validate and quantify the age‐related changes in gene expression observed by RNA‐sequencing in photoreceptor nuclei. From this, we can begin to ask questions about the role of epigenetic factors in regulating these changes in gene expression and how these factors are affected by aging.Support or Funding InformationNational Institutes of Health