The purpose of this BRP is to develop and evaluate new instrumentation that will permit unprecedented three dimensional imaging of single cells in the human retina, specifically rod and cone photoreceptors and ganglion cells. An interdisciplinary team will combine adaptive optics (AO), enabling the best lateral resolution for retinal imaging, with optical coherence tomography (OCT), providing the best axial resolution for retinal imaging. Two instruments will be developed using complementary OCT imaging modalities, flood illumination and enface scanning. These instruments will be used to study cellular morphology associated with normal aging, age-related macular degeneration (AMD) and glaucoma. The instruments will be compared quantitatively with each other and with existing retinal imaging devices. The project will be led by UC-Davis COCD), where a high-performance AO system has been developed in collaboration with the Lawrence Livermore National Laboratory (LLNL). This collaboration will be expanded to include a team of OCT experts at LLNL and Indiana University (IU). The IU team has previously collaborated with LLNL through the Center for Adaptive Optics and has already developed a working prototype AO-OCT system for retinal imaging. In this BRP project, LLNL will construct one AO-OCT instrument at the UCD site to be tested clinically in years 3-5, while the second AO-OCT instrument will be developed at IU in collaboration with LLNL and tested in the laboratory in years 4-5. Comparisons of AO-OCT and functional measures will be obtained at UCD and IU. Both instruments will be made available for use by scientists and clinicians who are not part of the BRP, and will be refined through the course of the project period. UCD has expertise in vision science, aging, and evaluation of AMD and glaucoma progression and treatment LLNL has a long history of research on AO for astronomy and has transferred some of its AO technology to vision science at UCD. LLNL also has expertise in OCT, and has pioneered its application to in vivo imaging of oral and vascular structures. The IU team has experience in AO-OCT and vision science with specific expertise in visual optics and retinal electrophysiology. This BRP is buttressed by consultants who have developed ophthalmic OCT technology at the University of Texas and Carl Zeiss Meditec. The Zeiss group has already transferred OCT technology to the clinic via commercial development and will facilitate incorporation of user friendly interfaces for our AO-OCT systems. This BRP thus combines the unique expertise of engineers, vision scientists and clinicians who have experience working together to effect a smooth transition from the laboratory to applications. This synergistic team will develop a new generation of instruments to advance vision science, permit retinal dysfunction to be studied in vivo in a way that will offer new insights into normal aging, the pathogenesis of glaucoma and macular degeneration, and a reliable method to monitor novel treatments for retinal disease.