# Calcium channels in retinal photoreceptors

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $379,137

## Abstract

Project Summary
The long-term objective of our research is to understand the Ca2+ signaling mechanisms that
regulate the development and mature function of the retinal circuitry. The overall objective of the
proposed research is to determine the modulatory impact of amyloid proteins on the first synapse
in the visual pathway formed between photoreceptors (PRs) and second order neurons, and how
this synapse may be disrupted in the context of Alzheimer’s disease (AD). Our focus will be on
Cav1.4 Ca2+ channels, which mediate Ca2+ signals needed for the release of neurotransmitters
from PR synaptic terminals, and are necessary for maintaining the structure and molecular
organization of the PR synapse. In rodent models of AD, Cav1 subtypes related to Cav1.4 are
significantly upregulated due to effects of amyloid b (Ab) aggregates that are the pathological
hallmark of AD and which are found to accumulate in the retina of mouse models of AD. Ab is
derived from processing of amyloid precursor protein (APP). APP and Ab have been shown to
cause the downregulation and upregulation, respectively, of Cav1 channels in neurons. Based on
these findings, and the retinal and visual phenotypes in AD mutant mouse strains, our central
hypothesis is that APP controls the normal presynaptic functions of Cav1.4 in PRs, and that
increasing load of Ab leads to upregulation of Cav1.4 and subsequent disruption of PR synapses
in the context of AD. Our specific aims are to: (1) Determine the effect of APP and Ab on the
properties of Cav1.4 and (2) Analyze the structural and molecular organization of PR synapses in
APP knockout mice and mouse models of AD. The expected outcome of our research is an
understanding of how amyloid proteins affect retinal Cav1.4 channels and PR synapses in normal
and diseased states of the retina. The broader impact of our research is the identification of
pathways that could shed light on visual phenotypes associated with AD and how the retina could
be used as a model system in which to study the synaptopathic mechanisms underlying this
disease, thus paving the way for novel disease-modifying therapies.

## Key facts

- **NIH application ID:** 10123424
- **Project number:** 3R01EY026817-04S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Sheila A Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,137
- **Award type:** 3
- **Project period:** 2020-04-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123424

## Citation

> US National Institutes of Health, RePORTER application 10123424, Calcium channels in retinal photoreceptors (3R01EY026817-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10123424. Licensed CC0.

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