# Mechanisms for Light-driven Chromophore Synthesis by Müller Cells to Regenerate Cone Opsin and Maintain Cone Sensitivity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $417,805

## Abstract

Project Summary / Abstract
The goal of this project is to identify three proteins of the intrinsic retinal visual cycle that maintain the
sensitivity of cones under daylight conditions. During the previous funding period, the PI found that co-
expression of RGR opsin and retinol dehydrogenase-10 (Rdh10) confers upon cells the capacity to take
up all-trans-retinol (atROL) from the medium and release 11-cis-retinol (11cROL), only on exposure to
visible light. The same atROL to 11cROL conversion activity has been observed by Müller cells,
although not previously reported as light dependent. Cones, but not rods, possess an 11cROL-
dehydrogenase (11cRDH) activity that allows them to utilize the 11cROL released by Müller cells to
make 11cRAL chromophore and thereby regenerate photobleached cone opsins. The long-term goal
of this project is to understand the processes that enable continuous cone vision during
daylight exposure in mammals. Given the importance of cones to human vision, addressing this
deficit in our knowledge is certainly within the NEI mission. Specific Aim 1 is to determine the roles of
RGR opsin and Rdh10 in the intrinsic retinal visual cycle. This will be accomplished in a collaborative
study using biochemical and physiological methodologies. The central hypothesis for Aim 1 is that RGR
opsin and Rdh10 comprise the 11cROL-generator in Müller cells, and that formation of 11cROL by
these proteins is driven by light. Specific Aim 2 is to identify the 11cRDH that allows cones to
regenerate visual pigment from 11cROL. This will be accomplished using a cDNA expression-screen to
test members of the short-chain dehydrogenase/reductase (SDR) family that are expressed in cones.
The expected outcome of this study is the identification of three proteins that together comprise the
intrinsic retinal visual cycle. These results amount to the uncovering of a new metabolic pathway in the
retina. They will greatly extend our knowledge about the regeneration of cone visual pigment in
daylight. Also, they will open the door to further genetic and functional biochemical studies into the
retinal visual cycle, including the potential to identify new susceptibility loci for inherited retinopathies
and maculopathies. Mutations in the human RGR gene have already been associated with retinitis
pigmentosa in a small subset of cases. While it has been long appreciated that invertebrates, such as
insects, use light to regenerate their visual pigments, this has never been shown for vertebrates. The
PI's finding that light drives regeneration of cone visual pigment is therefore a novel and
important discovery.

## Key facts

- **NIH application ID:** 10074567
- **Project number:** 5R01EY024379-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** GABRIEL H TRAVIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $417,805
- **Award type:** 5
- **Project period:** 2015-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074567

## Citation

> US National Institutes of Health, RePORTER application 10074567, Mechanisms for Light-driven Chromophore Synthesis by Müller Cells to Regenerate Cone Opsin and Maintain Cone Sensitivity (5R01EY024379-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074567. Licensed CC0.

---

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