# Spectral & Metabolic Basis of Visual Responses

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $429,355

## Abstract

The recovery of visual sensitivity during and following bright light (bleaching) exposure requires that the visual
pigment within rods and cones be regenerated quickly and efficiently to terminate the persistent activation of the
transduction cascade by the transient photoproducts of bleaching and opsin. Sensitivity recovery also requires
that activated rhodopsin, which is normally phosphorylated and bound by arrestin following light activation, be
dephosphorylated to return to the dark-adapted ground state. The reversal of these processes is slow, and their
role in sensitivity recovery is poorly understood. Here we propose to use a multidisciplinary approach, including
physiological and biochemical methods, on rod photoreceptors from transgenic mice to determine how rhodopsin
dephosphorylation and opsin adaptation impact the overall process of dark adaptation. We will focus on
elucidating the properties of two mechanisms. The first is rhodopsin dephosphorylation, a slow process that
occurs normally as regenerated visual pigment is returned to its dark-adapted ground state. The second is to
determine the role that free opsin plays in bleaching (opsin) adaptation. Photoreceptor sensitivity will be
measured electrophysiologically (single cell and electroretinogram recordings), the rate and extent of pigment
bleaching/ regeneration will be measured microspectrophotometrically, and rhodopsin phosphorylation will be
measured biochemically by immunofluorescence of differentially phosphorylated rhodopsin (isoelectric
focusing). There are three Specific Aims. In Aim I we will determine the cellular mechanisms that regulate
rhodopsin dephosphorylation in rod photoreceptors isolated from the retinal pigment epithelium, and following
exposure to bright light. These experiments will be based on our recent observation that the rate of rhodopsin
dephosphorylation is regulated in mouse rods by the oxygen and lactate content in the medium bathing the
retina. We will determine the relation of lactate and O2 to dephosphorylation, and whether they work singly or in
concert. We will then determine whether lactate and O2 work through controlling the NAD/NADP ratio in rods,
whether they act through Müller cells, or whether their effects are mediated through monocarboxylate
transporters. Experiments in Aim II will determine the dependence of the rate of recovery and/or the extent of
dark adaptation on lactate and O2. Experiments in Aim III will establish the phosphorylation state of free opsin
responsible for bleaching adaptation, and we will determine the extent to which phosphorylated and
unphosphorylated opsin activate transducin. Results of these studies will provide a molecular understanding of
those mechanisms of dark adaptation that are related to rhodopsin dephosphorylation and opsin adaptation to
provide insights into effective therapies for the treatment of blinding eye diseases.

## Key facts

- **NIH application ID:** 9954080
- **Project number:** 5R01EY001157-46
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** M CARTER CORNWALL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,355
- **Award type:** 5
- **Project period:** 1977-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954080

## Citation

> US National Institutes of Health, RePORTER application 9954080, Spectral & Metabolic Basis of Visual Responses (5R01EY001157-46). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9954080. Licensed CC0.

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