Prescribing the Molecular Message of Retinal Health
MentorRiccardo Natoli, PhD
To harness and deliver the natural homeostatic cargo of retinal exosome vehicle (EV) as a lowly-immunogenic and neuroprotective therapy for the treatment of age-related macular degeneration. Aim 1: To understand the role of retinal EV in health and degeneration, the bioavailability and molecular composition of retinal EV will be profiled using both rodent models of AMD as well as human AMD donor retinas. Aim 2: To determine the efficacy of microRNA-based therapeutics. Aim 3: To develop lowly-immunogenic treatment strategies for the treatment of AMD. Patient-derived EV will be therapeutically loaded with key homeostatic EV cargo including miRNA and delivered to the degenerating retina.
Our innovation is in harnessing the natural molecular cargo of retinal EV to develop therapeutics for AMD. To do this, we will load and deliver essential EV cargo using patient-derived EV, e.g. from blood or stem cells, to develop a lowly-immunogenic therapeutic platform by which patients can effectively "treat themselves." The use of autologous EV as a therapeutic delivery agent would not only reduce the risk of adverse immune reactions to the patient but would provide a more targeted and replenishable therapy that could be accessed and adapted over a patient's lifetime. The outcomes of this study will fill gaps in our knowledge of fundamental retinal biology and address unmet clinical needs that are holding back the field of EV therapeutics. By harnessing and delivering the "molecular message of health," this work will provide a framework for the development of EV-based therapeutics for the treatment of retinal degenerations, including the currently untreatable AMD. The development of this therapeutic pipeline can further be used in the treatment of neurodegenerative diseases and diseases in which EV dysregulation is a key pathogenic feature.