# Neutrophil driven recovery from traumatic and ischemic optic neuropathy

> **NIH NIH K08** · OHIO STATE UNIVERSITY · 2021 · $179,517

## Abstract

Abstract
Axonopathy is an early and prominent pathological feature of optic neuritis, ischemic optic neuropathy,
glaucoma, and traumatic optic nerve injury. Permanent loss of vision in all of these conditions is secondary, in
large part, to a failure of retinal ganglion cells (RGC), the output neurons of the optic nerve, to survive and
regenerate their axons. There is a dire need to develop novel therapeutic interventions that overcome barriers
to repair in the adult CNS and promote RGC survival and 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 transcripts for arginase-1 and CD206. In preliminary studies we
demonstrated that zymosan elicited Ly6GlowCD14+ neutrophils stimulate neurite outgrowth of dissociated RGC
in co-cultures in vitro. Furthermore, adoptive transfer of purified 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. The overall goals of the current proposal are to increase
our understanding of the pathways that underlie the intraocular accumulation and function of reparative
Ly6GlowCD14+ neutrophils, and to assess their efficacy in an alternative model of optic nerve damage. In Aim
1, we will interrogate the factors that promote the intraocular accumulation of Ly6GlowCD14+ neutrophils in our
model. We hypothesize that the chemokines involved differ from those that orchestrate the trafficking of
mature, conventional neutrophils. In Aim 2, we will determine the role of the arg1+ monocytes, that are
recruited to the eye following the initial entry of Ly6GlowCD14+ neutrophils, in RGC protection and axon
regeneration. In Aim 3, we will test our hypothesis that Ly6Glow CD14+ neutrophil mediated ocular repair
translates to another model of RGC injury, secondary to ischemia. 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 lost neurological functions in patients with optic
trauma or other conditions characterized by optic neuropathy.

## Key facts

- **NIH application ID:** 10239072
- **Project number:** 5K08EY029362-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Andrew Robert Sas
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $179,517
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239072

## Citation

> US National Institutes of Health, RePORTER application 10239072, Neutrophil driven recovery from traumatic and ischemic optic neuropathy (5K08EY029362-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239072. Licensed CC0.

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