# Regulation of vascular development in the eye by an opsin 5-dependent clock

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $478,648

## Abstract

Project Summary
We have recently published that light entrainment of the local circadian clock in the
retina is dependent on Opsin 5 (OPN5) and that Opn5 is expressed in a subset of retinal
ganglion cells (RGCs). In preliminary analysis we have also shown, (1) that mice
mutated for Opn5 or in clock genes (Per2 and Bmal1) have vascular development
defects in both the retina and hyaloid vessels, and (2) using ChIP-seq analysis, that the
vascular modulators Flt1 and EphrinB2 are directly regulated by the clock transcription
factor BMAL1. Based on these data, we propose a model to explain the mechanism by
which OPN5 regulates vascular development. In this model we suggest that light
stimulation of OPN5 in RGCs first entrains a circadian clock in the neurons of the inner
retina. We suggest that in turn, the clock transcription factor BMAL1 directly regulates
rhythmic expression of Flt1 and EphrinB2. Since these are crucial regulators of the
VEGFA (vascular endothelial growth factor A) response, this provides a direct link to the
regulation of retinal angiogenesis and hyaloid vessel regression. Our central hypothesis
is that an OPN5-dependent, local retinal clock regulates expression of Flt1 and
EphrinB2 and, in turn, light-dependent vascular development of the eye. To
investigate this hypothesis, we propose three aims. We will determine when during
development the OPN5-dependent retinal clock is first active (Aim 1), whether retinal
clock function is required for normal vascular development (Aim 2) and whether Flt1,
EphrinB2 and other vascular mediators are regulated by an OPN5-dependent retinal
clock. The existence of an OPN5-dependent pathway that regulates vascular responses
in the eye is an unusual finding that may have important implications for the human
vascular retinopathies.

## Key facts

- **NIH application ID:** 10000100
- **Project number:** 5R01EY027077-05
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Richard A. Lang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $478,648
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000100

## Citation

> US National Institutes of Health, RePORTER application 10000100, Regulation of vascular development in the eye by an opsin 5-dependent clock (5R01EY027077-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000100. Licensed CC0.

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