# Spectral & Metabolic Basis of Visual Responses

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $28,855

## 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:** 10051071
- **Project number:** 3R01EY001157-45S1
- **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:** $28,855
- **Award type:** 3
- **Project period:** 1977-04-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051071

## Citation

> US National Institutes of Health, RePORTER application 10051071, Spectral & Metabolic Basis of Visual Responses (3R01EY001157-45S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10051071. Licensed CC0.

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