NEI Audacious Goals Initiative: Translation-Enabling Models to Evaluate Survival and Integration of Regenerated Neurons in the Visual System (U24 Clinical Trials Not Allowed)

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The purpose of this FOA is to stimulate development of translation-enabling models for evaluating survival and integration of regenerated photoreceptors (PRCs) and retinal ganglion cells (RGCs) in model systems that are closer to human visual anatomy, function and/or disease than current models. The development of these models, tools, devices, novel therapies and/or other resources is expected to provide a resource to vision researchers developing cell-replacement therapies for visual system diseases and disorders. This FOA seeks to develop models that emulate critical aspects of a human blinding disease that might be amenable to regenerative therapy. The model system might involve specific defects generated by transgenic gene insertion and/or deletion, gene editing, chemical/physical means, and/or other approaches to emulate characteristics of human disease or create defects amenable to cell-replacement therapy. Model systems using non-human primates or other cone-dominant species that are more representative of the anatomy and physiology of the human retina are highly encouraged. Other biological models are acceptable provided they meet the overall objectives of the FOA. An important aspect of this FOA is that the research team is expected to treat the loss of vision associated with the experimental model using an approach that involves regenerating PRCs and/or RGCs and their connections. The choice of cells for therapy might include adult stem cells, precursors, stem cell derived progenitor cells, or conversion of intrinsic cells such as glia. It is expected that quantitative measures will be used to evaluate survival and integration of the regenerated cells using electrophysiology, functional imaging, behavioral measures or any other appropriate technology that would demonstrate circuit integration and restoration of visual function.

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