# Rebuilding visual functional connections

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $442,500

## Abstract

PROJECT SUMMARY
The damage or degeneration of the axons derived from the retinal ganglion cells (RGCs) in the optic nerve
accounts for the visual functional defects after traumatic injury or degenerative diseases such as glaucoma.
Thus, the logical repair strategy is to promote injured optic nerve axons to regenerate across the lesion and
reconnect with their targets. In the previous funding period, we have made significant progress in optimizing
regeneration-promoting strategies. We first discovered that co-deletion of PTEN and SOCS3 resulted in robust
axon regeneration. Our further studies showed that over-expression of osteopontin (OPN) and IGF1 and CNTF
could mimic the effects of co-deletion of PTEN and SOSC3, leading to similar extents of axon regeneration.
However, such regenerated axons fail to re-myelinate preventing recovery of vision unless potassium channel
blocker is acutely administered to allow axonal conduction of neuronal signal. Since OPN/IGF1/CNTF are all
extracellular proteins and recombinant proteins can be produced, this combination may be the most promising
treatment for stimulating RGC axon regeneration and vision function recovery. To further develop this into an
effective therapeutic strategy, we need to address the following issues: can OPN/IGF1/CNTF combination
stimulate all types of RGCs to regenerate axons? Do regenerated axons project to correct targets? How can
re-myelination be induced? Using the optic nerve and optic tract regenerative animal model, we will address
each of these questions, in a hope to reveal key cellular and molecular regulators these processes. We expect
that the obtained results might provide insights into develop more effective and safe therapeutic strategies of
promoting vision restoration.

## Key facts

- **NIH application ID:** 9881293
- **Project number:** 5R01EY021526-09
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ZHIGANG HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2011-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881293

## Citation

> US National Institutes of Health, RePORTER application 9881293, Rebuilding visual functional connections (5R01EY021526-09). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9881293. Licensed CC0.

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