# A novel inflammatory cell with neuroprotective and neuroregenerative properties

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $278,809

## Abstract

Axonopathy is an early and prominent pathological feature of many central nervous system (CNS) disorders,
including brain and spinal cord trauma, optic neuropathy, Multiple Sclerosis, early stage Alzheimer’s disease,
and subcortical ischemia. Poor clinical outcomes in all of these neurological conditions are due, in large part, to
the limited regenerative capacity of adult CNS neurons, including retinal ganglion cells (RGC, the neurons that
give rise to the optic nerve). There is a dire need to develop novel therapeutic interventions that overcome
barriers to repair in the adult CNS and promote axonal regrowth. The studies proposed here are based on our
discovery of a novel subset of pro-regenerative neutrophils, characterized by the cell surface phenotype
Ly6GlowCD14+, that accumulate in the posterior chamber of the eye or the peritoneal cavity following local
administration of the yeast cell wall extract, zymosan. These neutrophils bear a ring-form nucleus and express
high levels of pattern recognition receptor, dectin-1, as well as transcripts for arginase-1 and CD206. In
preliminary studies we demonstrated that adoptive transfer of zymosan-elicited Ly6GlowCD14+ neutrophils
directly into the vitreous of mice with optic nerve crush (ONC) injury is sufficient to rescue RGC from cell death
and to stimulate the regrowth of severed RGC axons. Furthermore, conditioned media harvested from cultures
of Ly6GlowCD14+neutrophils induce neurite outgrowth of dissociated RGC and dorsal root ganglion neurons in
vitro. The overall goal of the current proposal is to elucidate the pathways that underlie the differentiation,
survival and mechanism of action of these unconventional reparative neutrophils, and to leverage the
knowledge gained for the development of immunomodulatory therapies that mitigate, or even reverse, damage
to CNS neurons and axons. In Aim 1 we will test our hypothesis that transforming growth factor (TGF)- drives
the differentiation of Ly6GlowCD14+ neutrophils in vivo following the administration of zymosan. In Aim 2 we will
determine the role of hypoxia induced factor (HIF)-1 in the stabilization, survival and biological functions of
Ly6GlowCD14+ neutrophils. In Aim 3 we will optimize protocols for the generation of pro-regenerative
neutrophils from bone marrow precursors ex vivo. Selected neutrophil lines will be infused into mice with ONC
injury to assess their efficacy as an autologous cellular therapy. In addition, we will use proteomic and genetic
approaches to characterize the soluble factors present in Ly6Glow neutrophil-conditioned media that are
responsible for enhanced neurite outgrowth. A future direction will be to administer candidate
neuroregenerative factors to mice with axonopathy as disease modifying agents. We are hopeful that the data
generated by our study will ultimately lead to the development of innovative cell based therapies and/ or
immunomodulatory drugs with neuroprotective/ regenerative properties that restore...

## Key facts

- **NIH application ID:** 9900003
- **Project number:** 5R01EY029159-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Benjamin M Segal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $278,809
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900003

## Citation

> US National Institutes of Health, RePORTER application 9900003, A novel inflammatory cell with neuroprotective and neuroregenerative properties (5R01EY029159-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900003. Licensed CC0.

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