# Sigma-1 Receptor Provides Neuroprotection Against Optic Neuropathy

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2020 · $383,438

## Abstract

The goal of this project is to evaluate the effects of sigma-1 receptor (S1R) activation on RGCs and optic nerve
head astrocytes (ONHAs) under glaucomatous conditions. Glaucoma is the leading cause of irreversible
blindness worldwide and is characterized by the progressive degeneration of retinal ganglion cells (RGCs).
The major risk factor for glaucoma is increased intraocular pressure (IOP), and lowering IOP is currently the
only treatment strategy for this disease. However, in many cases, decreasing IOP does not effectively prevent
glaucomatous vision loss. Thus, novel therapies are needed. Activation of the multifunctional sigma 1 receptor
(S1R) is a promising pluripotent target for glaucoma treatment. S1R stimulation provides robust RGC
protection, both in vitro and in vivo, but it has not been tested in glaucoma. In addition, the mechanisms of
S1R-mediated neuroprotection are not well understood. S1R is a ligand-operated, transmembrane protein that
is expressed in RGCs and astrocytes throughout the visual system. A major deficit in our understanding of S1R
is knowledge of its direct effects on glia cells and how these effects mediate glia-neuronal interactions.
Astrocytes are the major glial constituent of the optic nerve head (ONH), which is the site of initial
glaucomatous injury. At the ONH, astrocytes play a critical role in maintaining the health of RGC axons. Our
preliminary data indicates that agonists of S1R can protect RGCs through cell autonomous effects on RGCs
themselves and through non-cell autonomous effects on optic nerve head astrocytes (ONHAs). We find
evidence that activation of S1R in ONHAs suppresses astrocyte reactivity and increases release of brain
derived neurotrophic factor (BDNF). In addition, previous studies show that S1R agonists not only protect
neurons from injury, but also enhance neuronal plasticity and restore neuronal function. In this proposal, we
will test the hypothesis that S1R agonists shift the balance of ONHA-mediated support functions in favor of
RGC protection. Thus, treatment of ocular hypertensive rats with S1R agonists is proposed to prevent and
restore structural and functional deficits in experimental glaucoma. To test our central hypothesis we propose
three specific aims:
Aim 1: Test the hypothesis that S1R agonists slow progression and rescue structural and functional deficits in
experimental glaucoma.
Aim 2: Test the hypothesis that S1R directly mediates ONHA reactivity and trophic factor secretion.
Aim 3: Test the hypothesis that S1R activation in ONHAs provides neuroprotection for RGCs.
.

## Key facts

- **NIH application ID:** 9853788
- **Project number:** 5R01EY027406-03
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Kathryn Bollinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,438
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853788

## Citation

> US National Institutes of Health, RePORTER application 9853788, Sigma-1 Receptor Provides Neuroprotection Against Optic Neuropathy (5R01EY027406-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853788. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*