# Retinoids in Vision

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $80,243

## Abstract

ABSTRACT
 Vision is one of the fundamental senses that enables the perception of the surrounding environment. In
humans, this process is initiated in the retina, which is lined with millions of photoreceptors expressing opsins
bound to the visual chromophore, 11-cis-retinal (11-cis-RAL). Absorption of a photon by the opsin-bound visual
chromophore causes its isomerization to an all-trans configuration. This initial photochemical reaction triggers
the activation of a signal transduction cascade that eventually leads to the transmission of visual information to
the brain, while the activated opsin is rendered insensitive to further light stimulation. Sustained vision thus
requires continuous renewal of the visual chromophore following light exposure, a process thought to be
accomplished through the canonical retinoid (visual) cycle. Here, we propose to explore a non-canonical
complementary pathway for the photic generation of 11-cis-RAL. Our long-term goal is to obtain a better
understanding of the retinoid cycle and other pathways capable of regenerating the visual chromophore and to
develop interventions that stop the progression of human retinal diseases related to these metabolic events.
 Accordingly, we propose four thematically and experimentally linked Specific Aims to: 1) improve our
mechanistic insights regarding a photochemical reaction catalyzed by retinal pigment epithelium (RPE)-retinal
G protein-coupled receptor (RGR) that can generate 11-cis-RAL. We will determine the quantum yield (Φ) of
recombinant RGR and compare its rate of photoisomerization with the activity of RPE65, the enzymatic
isomerase of the RPE visual cycle. We also will test the influence of retinol dehydrogenase (RDH) and cellular-
retinaldehyde-binding protein (CRALBP encoded by Rlbp1 gene) as modulators of the RGR-based
photoisomerase activity; 2) determine the role of RGR in RPE and Müller cells (MC). To accomplish this
objective, we will investigate conditional Rgr-/- mice that permit the temporal regulation of the expression of RGR;
3) establish the contribution of RPE and MC separately to both the visual cycle as well as the photochemical
production of 11-cis-RAL using the traceable artificial chromophore 9-cis-RAL; and 4) establish the role of
CRALBP in RPE and MC during the regeneration of rod and cone visual pigments, by employing genetic and
pharmacological approaches. We will evaluate the effects of RPE/MC-specific Rlbp1 deletion on the
regeneration of rod and cone visual pigments, along with photoreceptor function in the presence and absence
of potent inhibitors of RPE65.
 In summary, recent advances pertaining to the photic generation of 11-cis-RAL in the RPE have added a new
and novel physiological element to our understanding of the cellular pathways capable of regenerating the visual
chromophore. However, these advances have yet to be fully integrated with what we know about the canonical
visual cycle. Here, we will provide a more unified perspective o...

## Key facts

- **NIH application ID:** 10685657
- **Project number:** 3R01EY009339-34S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Krzysztof Palczewski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $80,243
- **Award type:** 3
- **Project period:** 1992-08-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685657

## Citation

> US National Institutes of Health, RePORTER application 10685657, Retinoids in Vision (3R01EY009339-34S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10685657. Licensed CC0.

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