Project Summary/Abstract Ganglion cells (GCs) and other inner retinal neurons are fundamental to retinal neural circuitry, processing photoreceptor signals relayed from intermediate neurons for transmission to the brain. Yet, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. GCs in particular are lost to neurodegenerative disorders such as glaucoma, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. We also know from histology that a small fraction of these cells die each year as part of the normal aging process. Unfortunately, techniques to assess population loss and general health of GCs and other inner retinal neurons in vivo are limited. New optical modalities that are rapid, specific, and non-invasive promise to greatly enhance our ability to monitor the spatial and temporal dynamics of inner retinal neurons. This study takes advantage of unique optical instrumentation developed in my laboratory that combines adaptive optics and optical coherence tomography to achieve cellular-level 3D imaging of the living human retina. We will use this technique to investigate three specific aims that quantify the spatial properties of inner retinal neurons and their change in aging and glaucoma. The long term goal of this research is to establish high resolution, high specificity optical techniques as valid tools for probing structure and physiologic processes of the retina at the cellular scale. The resulting ability to study cells in vivo will improve early detection of and treatment monitoring for diseases that impact the retina.