# Reprogramming Strategies of Promoting Optic Nerve Regeneration and Vision Restoration

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

## Abstract

Project Summary
The damage of optic nerve axons prevents the relay of the visual information from the eye to the brain, leading
to the loss of vision. Therefore, our research has been focusing on developing methods to promote efficient
optic nerve axon regeneration and to re-build functional visual pathways. Recent studies have led to the
developments of several novel strategies that stimulate axon regeneration, however each of these methods
only achieved regeneration in subsets of retinal ganglion cells (RGCs). Thus, to restore vision, new strategies
are pressingly needed to promote regeneration of multiple types of RGCs. Inspired by the transcriptional
reprogramming technology for obtaining iPS cells, we hypothesized that over-expressing certain transcription
factors in adult RGCs could reprogram them into a young-RGC-like growth competent state. To this end, we
have performed a screen for a list of transcription factors that are normally expressed during the differentiation
stage of retinal progenitor cells, to examine which one(s), when overexpressed in adult RGCs, could enable
significant axon regeneration using an intraorbital optic nerve injury model. Interestingly, we found that forced
expression of the transcription factor Sox11, and to a less extent Sox4, resulted in marked optic nerve
regeneration. Preliminary analysis revealed that the effects of Sox11 are likely different from those triggered by
PTEN deletion (see Approach). Furthermore, while PTEN deletion promotes the regeneration selectively from
alpha type of RGCs, Sox11 overexpression promotes the regeneration of melanopsin-expressing intrinsically
photosensitive RGCs (ipRGCs) and other un-determined types of RGCs. These initial findings suggested a
novel rationale for promoting optic nerve regeneration by reinstitute Sox11 expression. Here, we propose to
explore the underlying mechanisms by which Sox11 stimulates RGC axon regeneration and its potential
application, either by itself or in combination with others, in achieving functional recovery.

## Key facts

- **NIH application ID:** 9989124
- **Project number:** 5R01EY026939-05
- **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:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989124

## Citation

> US National Institutes of Health, RePORTER application 9989124, Reprogramming Strategies of Promoting Optic Nerve Regeneration and Vision Restoration (5R01EY026939-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989124. Licensed CC0.

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