Adaptive optics imaging and micro-stimulation to yield in vivo single-cell biomarker of retinal function and dysfunction in the human retina.

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Current clinical retinal imaging and function testing in subjects suffering from degeneration of the neuro-retina is not sensitive enough to pick up small but significant physiological changes within time frames that would be feasible for evaluation of emerging gene and cell based intervention efforts. We aim to close this gap with recently developed imaging and stimulation technology that utilizes adaptive optics (AOSLO) to visualize and target retinal locations on a microscopic level in vivo. Specifically, as a consequence of neuro-degenerative processes, the individual cells of the photoreceptor mosaic may show functional changes (e.g. in their sensitivity to light) before a structural change (e.g. cell loss) is detected. We will develop photoreceptor-resolved functional tests that probe the relationship of retinal structure and function directly and on a cellular scale. These AOSLO-based results may act as sensitive biomarkers of retinal integrity that can be used to better understand disease mechanisms and to track and predict relevant cellular changes during its progression and intervention. If successful, in vivo cellular function testing with AOSLO lessens the need of inefficient, protracted histological validation in the development phase of new treatments, because microscopic physiological changes can be monitored in real-time within the living subject. We will make our results and methods available for other researchers within the SPP as a platform to test newly developed and future therapeutic approaches in treated subjects directly.