PROJECT SUMMARY Disruptions in retinal structures are largely thought to contribute to reduced visual function. The diagnosis and management of diseases which cause disruptions in retinal structures relies on the ability to non-invasively assess the living retina. Adaptive optics (AO) based imaging tools have enabled visualization of retinal structure at the cellular level and have enabled high resolution functional testing. However, previous AO-centric studies have classically evaluated retinal structure and function independently. This results in a significant gap in our understanding of how variations in retinal structure in turn impact measures of retinal function. Closing this gap is essential for advancing functional assays and improving our understanding of how disruptions to retinal structures impact visual function. Here, we will explore the relationship between retinal structure and function in vivo using an adaptive optics scanning light ophthalmoscopy (AOSLO) based psychophysical task to measure AO-corrected visual acuity in individuals with disruptions to their retinal structure caused by albinism. We will also improve our understanding of a new functional assay for probing individual photoreceptor cells, intensity based optoretinography (iORG), by quantifying how natural variation in the eye that occurs throughout the day due to circadian rhythm, and how different spectral cone types contribute to variations seen in this signal. We will accomplish this through the following two aims: Aim 1) examine how disruptions in foveal anatomical specializations impact visual function using AOSLO-based tools. Through investigating the relationship between the Nyquist sampling limit of the foveal photoreceptor mosaic and adaptive optics corrected visual acuity in individuals with albinism I hope to gain important insight on if disruptions to foveal private line circuitry could drive the variable visual acuity reported in these individuals; Aim 2) characterize factors which cause variation in iORG measurements in individual and populations of cones. In order to improve iORG and gain a better understanding on how experimental procedures such as the time day in which data was collected and the distribution of different spectral cone types impact variations in iORG metrics we will investigate the degree to which these factors contribute to variations seen in iORG signals. Completion of this research project will provide insight on how variations in retinal structures impact visual function in living humans. In addition, this project will improve a diagnostic tool (iORG) which can be used to probe individual photoreceptor function in vivo. Beyond the scientific advancements this research seeks to accomplish, this also presents a unique training opportunity which combines retinal imaging, optics, software development, engineering principles, and clinical experience. The proposed research training plan will provide me with valuable technical, research,...