PROJECT SUMMARY /ABSTRACT Age-related degeneration of the retinal vasculature is one of the most pervasive developments in the aging eye, resulting in increased susceptibility to vision threatening ocular diseases. Diabetic retinopathy in many ways manifests as accelerated aging. Despite extensive research, quantitative data describing the dynamic changes that occur during normal aging of the human retinal vasculature are limited. Appreciation of individual variability in groups of healthy aging controls is critical for accurate interpretation of clinical results and planning research into new treatment strategies. Thus, there is a desperate need for quantitative normative data describing retinal vascular changes in the aging population. Such data will provide age-matched reference values for retinal vasculature measurements. Our central hypothesis is that this normative data is essential for understanding the impact of age-related changes on the progression of retinal vascular diseases, in order to successfully identify more sensitive and predictive biomarkers. The most advanced currently available noninvasive imaging techniques, adaptive optics scanning light ophthalmoscopy and optical coherence tomography angiography, will be used to study structure and function of the human retinal microvasculature in aging controls, and subjects with diabetic retinopathy. Three linking hypotheses will be evaluated for their ability to support our central hypothesis, (1) advancing our current in vivo imaging techniques, which allow the unprecedented ability to image and monitor the vascular cells down to the capillary level, can be used to document precise quantification of structural and functional features of aging and diseased retinas, (2) there are microvascular changes occurring in the healthy aging retina which need to be identified and accounted for in any evaluation of retinal vascular pathology, and (3) subclinical retinal changes in diabetic patients detectable using these imaging techniques that can be used to help differentiate pathology and distinguish changes from those which characterize normal aging. It is hoped that the knowledge generated by the proposed project will provide meaningful microvascular metrics and interpretations for translation to clinical care.