# Development of Optic Nerve Relays to Restore Retinofugal Connections

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $245,402

## Abstract

Project Summary/Abstract
Optic neuropathies and retinal diseases are leading causes of irreversible blindness worldwide. Currently,
there are no therapies to restore vision loss. Whole eye transplants could restore vision if the neural circuits
between the eye and the brain could be restored. The long-term goal of this proposal is to develop therapies
that regenerate lost retinofugal pathways and enable whole eye transplants. In experimental models of central
nervous system injury, neural stem cells (NSCs) have been used to form neuronal relays that restore injured
connections and function. Preliminary data suggests that NSCs similarly integrate with the injured visual
system. The central hypothesis is that stem cell-derived neurons transplanted into the optic nerve can restore
function by receiving inputs from the eye and extending long-distance axonal projections. This proposal will
test this hypothesis by pursuing the following specific aims: 1) identify the optimal donor cell type to establish
optic nerve relays, 2) optimize survival of host RGCs using gene editing in conjunction with an optic nerve
relay, and 3) evaluate the degree to which optic nerve relays adjacent to terminal targets form synapses. The
proposed studies are significant because they develop a novel use of stem cells to form neuronal relays to
achieve robust, long-distance axonal regeneration and enable whole eye transplants. The positive translational
impact is the potential development of therapeutic strategies that restore vision, including whole-eye
transplants.
This K08 grant will allow Dr. Jiun Do, M.D., Ph.D. to obtain the scientific training and professional skills to
establish a research program focused on optic nerve regeneration and become an independent investigator.
To facilitate achieving this goal, Dr. Do has assembled an exceptional mentoring team at UCSD consisting of
Dr. Mark Tuszynski, M.D., Ph.D., an expert in neuroregeneration and neural stem cell therapies in the spinal
cord, and Dr. Derek Welsbie, M.D., Ph.D., an expert on retinal ganglion cell degeneration and neuroprotection.
This is complemented by an external clinician-scientist committee that includes Drs. Zhigang He, Ph.D. and.
Larry Benowitz, Ph.D., experts in optic nerve regeneration and successful scientists in vision research. Key
components of this training plan include: 1) acquisition of scientific and technical expertise to develop stem cell
technologies and modify the visual system, 2) formal didactic courses and training in grant writing, ethics, stem
cell biology, and gene editing, 3) generation of data for an R01 submission, and 4) planned transition to
independence through mentorship. This work takes place at UCSD, an outstanding research environment and
world class facility, and in the Department of Ophthalmology, which has a strong track record of producing
successful clinician-scientists. Combined with his clinical training in glaucoma, this career development plan
will allow Dr. ...

## Key facts

- **NIH application ID:** 10683977
- **Project number:** 5K08EY033032-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jiun Lap Do
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $245,402
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683977

## Citation

> US National Institutes of Health, RePORTER application 10683977, Development of Optic Nerve Relays to Restore Retinofugal Connections (5K08EY033032-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10683977. Licensed CC0.

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