# Molecular Mechanisms of Photoreceptor Adaptation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $417,380

## Abstract

Project Summary
 Our sense of vision begins when single rod and cone photoreceptors absorb light and produce an
electrical signal, which higher centers in the brain then analyze to alter our behavior. We learn even as
children that rods are the photoreceptors we use to see dim light and cones to see bright light and color. This
view is supported by behavioral measurements and electrical recording, which all seem to show that rods are
primarily used to detect dim light and become essentially non-functional as the ambient illumination increases
during daylight. Recent experiments have however challenged this notion and demonstrated that rods can
continue to respond even in light so strong that a large fraction of the rod photopigment is bleached. These
observations challenge our understanding of rod function in bright light. The purpose of this study is to
thoroughly reexamine rod current and voltage responses to persistent bright illumination over extended
durations of time. Our preliminary evidence shows surprisingly that the responsiveness of rods can recover
over the course of hours during persistent bright illumination. Here we are seeking to investigate the
molecular and mechanistic basis of this rod recovery and its dependence on time and light intensity in mice.
In particular, we will leverage several lines of transgenic mice having targeted mutations in components of the
phototransduction cascade. We also are interested in how photoresponse recovery in rods can be made
faster and more robust, as observed in cones. We we will explore these phenomena by genetically
transferring certain molecular features of cone phototransduction into the rods by leveraging mice with
targeted mutations to reduce the sensitivity of rods and increase the rate of photoresponse and photopigment
decay. We hope to show which factors are responsible for the differential responsiveness of the two
photoreceptors in bright light. These phenomena are not only important to our understanding of the
physiology of photoreceptors, they are also essential for photoreceptor survival because rods die when outer-
segment channels remain closed for too long a time. In addition, understanding how to make rod
photoreceptors more like cones may have therapeutic value, as deficiencies in cone vision may be mitigated
by shifting the responsiveness of rods to brighter background light intensities. Because of the importance of
these phenomena to photoreceptor function in health and disease, the Retinal Disease Program of the NEI
has as one of its program objectives to “analyze the mechanisms underlying light adaptation and recovery
following phototransduction”.

## Key facts

- **NIH application ID:** 9878868
- **Project number:** 5R01EY029817-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Alapakkam P Sampath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,380
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878868

## Citation

> US National Institutes of Health, RePORTER application 9878868, Molecular Mechanisms of Photoreceptor Adaptation (5R01EY029817-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878868. Licensed CC0.

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