# Opioid-Induced RGC Neuroprotection via Changes in Protein Acetylation

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $373,750

## Abstract

Glaucoma, a leading cause of blindness worldwide, is characterized by progressive loss of retinal ganglion
cells (RGCs), an excavated appearance of the optic nerve, and vision loss. The etiology of glaucoma is
complex, involving biomechanical and ischemic stress, neurotrophic factor deprivation, glial activation, and
enhanced production of pro-inflammatory cytokines. Currently, there is no clinical treatment to rescue RGCs in
glaucoma patients. Therefore, effective neuroprotective strategies and agents are needed to rescue RGCs in
this disease.
Our laboratory has demonstrated that sustained activation of δ-opioid receptor for 7-days offered significant
long-term (42-days) RGC neuroprotection in a chronic rat glaucoma model. This long-term neuroprotective
response supports the idea that opioids induce epigenetic changes in the retina and optic nerve allowing RGCs
to maintain their functional integrity under conditions that normally lead to progressive neuronal loss. Pain
management studies have shown that epigenetic changes are associated with opioid-induced tolerance and
dependence that develops following chronic opioid-administration. Two central events are responsible for
these opioid-induced epigenetic changes: an increase in histone acetylation, and prolonged elevation in
cAMP. We provided preliminary data showing that protein acetylation, levels of cAMP, and phosphorylation of
cAMP response element binding protein (CREB) are significantly reduced in ocular-hypertensive eyes.
Chronic δ-opioid administration increases the level of histone-H3 acetylation, stimulates cAMP/CREB
signaling, and eventually increases the expression of neurotrophins. Based on these benchmark preliminary
data, we hypothesize that: "Activation of δ-opioid receptors induces epigenetic changes that attenuate
glaucomatous injury”. To test this hypothesis, we propose two Specific Aims. 1) Determine the roles of
protein acetylation in the neuroprotective response to δ-opioid agonist and 2) Determine the role of CREB
signaling in the neuroprotective response to δ-opioid agonist. The outcome of the proposed studies will not
only have a positive impact on the understanding of mechanisms underlying the opioid-mediated RGC
neuroprotection, but will also identify new and novel neuroprotective strategies for the treatment of glaucoma
patients.

## Key facts

- **NIH application ID:** 9942409
- **Project number:** 5R01EY027355-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Shahid Husain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,750
- **Award type:** 5
- **Project period:** 2017-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942409

## Citation

> US National Institutes of Health, RePORTER application 9942409, Opioid-Induced RGC Neuroprotection via Changes in Protein Acetylation (5R01EY027355-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9942409. Licensed CC0.

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