# Optic Nerve Relays for Vision Restoration and Advancement Optic Nerve Regeneration Research

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $499,116

## 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 spinal cord injury
models, neural stem cells (NSCs) have been used to form neuronal relays that restore injured connections and
function. Similarly, NSCs have demonstrated the capacity to form neuronal relays in the optic nerve and
integrate into the injured visual system. The overall objectives in this application are to (i) determine the degree
of visual function recovery from long-term NSC-derived neuronal relays in the injured optic nerve and (ii)
develop methods to guide neuronal relay axons through the optic chiasm and to appropriate synaptic targets.
The central hypothesis is that stem cell-derived neurons transplanted into the optic nerve form neuronal relays
that can be guided to appropriate targets to restore vision-related function. This proposal will test this
hypothesis by pursuing the following specific aims: 1) measure the functional recovery from long-term optic
nerve grafted NSCs in the injured visual system, 2) investigate the role of canonical chiasmal guidance cues
on neuronal relay axon guidance, and 3) target neuronal relay axons to host vision-associated nuclei. In the
first aim, rodent optic nerve transection models will be treated with NSCs to restore retinofugal connections
with neuronal relays. Long-term integration and function of NSC-derived neuronal relays in restoring vision will
be evaluated with visual function testing and histological assessments for the structural indicators necessary
for effective neuronal relay conduction. For the second aim, NSCs with genetic modifications of canonical optic
chiasm guidance pathways that are important in development will be transplanted into a rodent optic nerve
transection model. These modified NSCs will be used to assess the effect of developmental guidance cues
that persist in the adult optic chiasm on the decussation of growing axons in the injured visual system and the
manipulability of those pathways. In the final aim, transduction of vision-associated nuclei to express
neurotrophins using an adeno-associated virus will be used to guide NSC-derived optic nerve neuronal relay
axons to innervate specific targets and facilitate recovery of visual function. The research proposed is
innovative because it overcomes current limitations in optic nerve regeneration by leveraging stem cells and
enables research on important downstream considerations necessary for successful optic nerve regeneration.
The proposed studies are significant because they develop a novel use of stem cells to form neuronal relays to
regenerate the optic nerve and adv...

## Key facts

- **NIH application ID:** 10869137
- **Project number:** 1R01EY036155-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jiun Lap Do
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $499,116
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869137

## Citation

> US National Institutes of Health, RePORTER application 10869137, Optic Nerve Relays for Vision Restoration and Advancement Optic Nerve Regeneration Research (1R01EY036155-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869137. Licensed CC0.

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