# Opioid Modulation of Retinal Ganglion Cells Providing Photoentrainment of the Circadian Clock

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2021 · $362,590

## Abstract

Abstract
Chronic pain (CP) is a cardinal feature of a diverse spectrum of diseases including
arthritis, migraine, cancer, metabolic disorders, and neuropathies; it afflicts at least 20–
30% of Americans. Opioids remain the pharmacological cornerstone of CP therapy,
despite potentially harmful side effects. In addition to the high propensity for developing
opioid addiction, insomnia-type sleep problems associated with daytime sleepiness and
depression occur in approximately 90% of those receiving long-term opioid treatment to
reduce suffering from CP. Importantly, sleep disorder is a serious risk factor for suicidal
ideation in CP patients receiving opioid therapy. Therefore, understanding the cellular
mechanisms and neuronal circuits contributing to sleep disturbances associated
with long-term opioid therapy in those suffering from chronic pain is absolutely
critical for determining whether sleep disruption is a modifiable risk factor for
suicidal ideation.
Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs)
projecting to the suprachiasmatic nucleus and other sleep-promoting brain centers are
the principal conduits responsible for photoentrainment of sleep/wake cycle. We
found that ipRGCs express µ-opioid receptors (MORs) and our preliminary data
shows that MOR specific agonists strongly attenuate light-evoked firing of ipRGCs.
Strong evidence suggests that systemically applied opioids cross the tight blood/retina
barrier and reach ipRGCs. The objectives of the current proposal are to analyze how
opioids alter light-evoked activity of ipRGCs and to study the behavioral consequences
of opioid modulation of ipRGC-mediated photoentrainment of circadian sleep/wake
cycles. The results of this project will provide a mechanistic description of a novel neural
pathway by which systemically administered opioids alter light-driven behavior, including
sleep/wake cycle. Additionally, the data will predict the feasibility of using MOR selective
antagonists for focal targeting of MORs expressed by ipRGCs to reduce the severity and
inherent comorbidities of sleep disorders in patients receiving long-term opioid therapies.

## Key facts

- **NIH application ID:** 10200064
- **Project number:** 5R01EY029227-03
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Jozsef Vigh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $362,590
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200064

## Citation

> US National Institutes of Health, RePORTER application 10200064, Opioid Modulation of Retinal Ganglion Cells Providing Photoentrainment of the Circadian Clock (5R01EY029227-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200064. Licensed CC0.

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