Nanoparticle-Based Tracking of Retinal Ganglion Cell Transplant

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Project Summary/Abstract There is a critical need to translate retinal ganglion cell (RGC) therapies from lab to clinic, particularly cell transplant therapies to repair degenerated eye tissues and restore visual function. RGC transplant has great potential in treating degenerative retinal and optic nerve diseases, but key pre-clinical studies are hampered by an inability to track transplanted cells. In this project, the candidate proposes to advance RGC transplant in treating glaucoma through longitudinal and non-invasive tracking of RGCs with the aid of nanoparticle-based optical coherence tomography (OCT) contrast agents. These nanoparticles are to be customized to label and visualize RGCs with a high spatial resolution. Longitudinal tracking of the RGCs in vivo could uncover the fate of the donor RGCs, increase our understanding of their behavior in the eye, and identify the factors that affect the treatment efficacy of RGC transplants. In this application, the PI first proposes to use spectral OCT signals of gold nanorods (GNRs) to maximize the contrast between donor RGCs and the retina in OCT imaging. Second, the PI proposes to examine the correlation between the OCT signals of GNRs and the fate of donor RGCs with both in vitro and in vivo assays. Third, the PI proposes to test the effects of cell number and injection location on the transplant success rate, and to leverage advanced imaging to optimize RGC transplantation. Overall, investigations in GNR-based OCT contrast agents for in vivo RGC tracking will gain us essential knowledge in the efficacy of RGC transplant and advance RGC transplant for glaucoma treatment. These data will contribute to the PI’s overall career goals, to investigate biomaterials that could track, support, and control therapeutic cells in vivo and to use these biomaterials to provide novel methods to treat otherwise incurable diseases. During the mentored phase of this award, the candidate will prioritize undertaking activities to increase understanding and gain hands-on training in the areas of OCT and glaucoma in the Department of Ophthalmology at Stanford, with support from the world-class Molecular Imaging Program and the outstanding Materials Science & Engineering Community at Stanford, and with the benefits of a close-knit and focused department and the multi- interdisciplinary collaborations and resources of the more comprehensive university.