Recent studies in Alzheimer?s Disease (AD) patients report localized retinal thinning and A? inclusions in the neurosensory retina, suggesting the eye?s utility as a non-invasive indicator of brain health. However, variation in methodologies between studies and other retinal complications due to other diseases and age limit the use of the retina as a potential AD biomarker. A comprehensive micro-level analysis of the retina is necessary to validate macrolevel clinical assessments. To identify potential biological mechanisms related to AD-associated retinal altercations, we will conduct a transcriptomic analysis of topographic and anatomical regions of retinal tissue from the left eye of autopsy-confirmed cases alongside age-matched non-diseased tissue. Retinal tissue from the right eye of the same AD case will undergo histopathological assessment for altercations of retinal structure and morphology to correlate changes in gene expression with retinal pathology. Secondly, we will use single-cell transcriptomics to identify specific retinal subpopulations impacted by AD. We hypothesize that AD- associated transcriptional alterations will localize to retinal subpopulations implicated in AD retinal pathology such as retinal ganglion cells and provide context to the retinal thinning observed in AD patients. Brain tissue from the corresponding AD case will be stained through in situ hybridization for transcripts identified through bulk and single-cell RNA-seq analysis to correlate AD brain pathophysiology to AD retinal disease progression. Results from these studies would provide additional mechanistic insight into the retinal thinning observed in AD and provide vital context to assess the feasibility of using the retina as a biomarker for AD disease progression.
The molecular mechanisms underlying AD-induced retinal changes is not well understood. We propose to examine AD retinal susceptibility through transcriptional profiling as well as conventional retinal techniques. Our goal is to objectively validate retinal changes in AD as well as provide a curated resource to identify candidate genes potentially involved in AD-mediated retinal changes.
