# Functions of OPN5 and OPN3 in the eye

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $536,170

## Abstract

PROJECT SUMMARY/ABSTRACT
 Circadian rhythms are the near-24-hour rhythms of physiology ubiquitous to almost all
eukaryotic life. Dysfunction of circadian rhythms underlies a variety of common sleep disorders and is
thought to contribute to other conditions ranging from psychiatric disease to cancer. The mammalian
retina serves a critical function in synchronizing the master circadian pacemaker (the suprachiasmatic
nucleus) to the daily light-dark cycle. Work over many years has also demonstrated that the retina itself
is a strong circadian oscillator. Indeed, many critical retinal functions, including visual sensitivity, the
pupillary light reflex, the electroretinogram, and the expression of hundreds of retinal genes, are under
strong circadian control; and that loss of retinal circadian rhythms results in impaired retinal function.
Our preliminary data have demonstrated that: 1) the retinal circadian clock can be entrained to light-
dark cycles in culture ex vivo, 2) this entrainment is not dependent on the classical rods and cones or
the melanopsin-expressing, intrinsically-photosensitive retinal ganglion cells, 3) the orphan opsin
neuropsin (OPN5) is necessary for this photoentrainment, and the orphan opsin encephalopsin (OPN3)
affects this process, 4) the retina utilizes a light-dependent, diffusible substance to synchronize its
rhythms, and 5) the cornea also contains a circadian clock which, remarkably, can be entrained to light-
dark cycles as well via an OPN5-dependent mechanism. We propose experiments to elucidate the
signaling mechanisms of OPN5 and OPN3; experiments to characterize the diffusible signal(s)
emanating from the retina, and experiments to elucidate the mechanism by which non-retinal tissues in
the eye maintain circadian rhythmicity and entrain to light-dark cycles. These data will provide a critical
basis for understanding how the circadian clock modulates retinal function as well as mechanistic
insights into two novel ocular photoreceptors.

## Key facts

- **NIH application ID:** 10176501
- **Project number:** 5R01EY026921-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Russell N. Van Gelder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $536,170
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176501

## Citation

> US National Institutes of Health, RePORTER application 10176501, Functions of OPN5 and OPN3 in the eye (5R01EY026921-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10176501. Licensed CC0.

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