# Developing new strategies to promote axon myelination for vision restoration

> **NIH NIH F32** · BOSTON CHILDREN'S HOSPITAL · 2021 · $64,875

## Abstract

PROJECT SUMMARY
In the United States, millions of people suffer from glaucoma and atypical optic neuritis, which causes irreversible
blindness due to the death of retinal ganglion cells (RGCs) and their projecting axons. For the past decade, the
field has focused on promoting RGC survival and axonal regeneration. Despite great strides in these two areas,
we have uncovered a new hurtle to restoring these neural circuits: regenerating RGC axons are not myelinated.
Myelin is essential for efficient axonal conduction, and it provides important support for the long-term survival of
regenerating axons. This myelination failure represents an underappreciated and essential aspect for the
restoration of functional vision recovery. Oligodendrocyte precursor cells (OPCs) are a progenitor population that
exist within the central nervous system (CNS), and are responsible for the generation of myelination-competent
oligodendrocytes throughout adulthood. However, our regeneration data shows that the presence of axons alone
is not sufficient to elicit myelination, and suggests the existence of an extrinsic barrier to OPC maturation. Using
the mouse optic nerve crush (ONC) model, we found that chronically activated microglia inhibit the maturation
of OPCs into myelinating oligodendrocytes. The elimination of microglia after ONC, using pharmacological
methods, allows for an unprecedented rate of myelination. However, premature elimination of microglia, prior to
ONC, results in a loss of OPC proliferation and is severely detrimental to myelination. Therefore, activated
microglia are simultaneously responsible for promoting and inhibiting distinct aspects of OPC development after
injury. To better understand this phenomenon, I will conduct single cell RNA sequencing (Smart-Seq2) on OPC
lineage cells after ONC, and in the presence or absence of activated microglia. I can then examine the rate of
oligodendrocyte maturation, and the effect of extrinsic inhibition from microglia on the transcriptomic profiles of
OPC lineage cells. In addition, I will sequence activated microglia after ONC to identify candidate molecules that,
when inhibited, could increase oligodendrocyte maturation and myelination. Candidate molecules will be
examined in vivo using viral vector knockdown strategies to test their efficacy in promoting the myelination of
regenerating axons after injury. This project holds the potential to identify new signaling pathways between
activated microglia and maturing oligodendrocytes that prevent the myelination of axons in an inflammatory
context. These findings will provide key insights for vision restoration after optic nerve injury or disease, and they
could also help promote the remyelination of axons in patients suffering from other CNS disorders, such as
multiple sclerosis and leukodystrophies. Dr. Zhigang He's lab and the F.M. Kirby Neurobiology Center at Boston
Children's Hospital are incredibly collegial and well-equipped institutions that will suppor...

## Key facts

- **NIH application ID:** 10234777
- **Project number:** 1F32EY032779-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Tracey Amelia Claire Sampath Suter
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $64,875
- **Award type:** 1
- **Project period:** 2021-05-01 → 2022-04-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234777

## Citation

> US National Institutes of Health, RePORTER application 10234777, Developing new strategies to promote axon myelination for vision restoration (1F32EY032779-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234777. Licensed CC0.

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