# Calcium channels in retinal photoreceptors

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $476,484

## Abstract

The long-term goal of our research is to understand how the properties of Cav channels shape their
neural functions. The objective of this competing renewal application is to define the Cav1-dependent
signaling pathways that shape the development and plasticity of the photoreceptor (PR) synapse. Among
the major Cav1 subtypes expressed in the retina, Cav1.4 is uniquely critical for PR synaptogenesis. How
Cav1.4 contributes to this process remains a mystery—a major challenge being that available animal
models do not distinguish between the roles of Cav1.4 as a source of Ca2+ ions and as a scaffold for
synaptogenic proteins. To overcome this hurdle, we generated a knock-in mouse strain expressing a non-conducting mutant form of Cav1.4. While the molecular organization of PR synapses is largely spared in
these mice, the maturation of synaptic ribbons and invagination of postsynaptic neurites into PR terminals
is disrupted. Our findings raise the intriguing possibility that the clinical variability associated with CSNB2
could arise from heterogeneous impacts of the mutations on the organization, development, and mature
function of the PR synapse. Our central hypothesis is that Cav1.4 mediates Ca2+ signaling pathways that
promote the maturation of synaptic ribbons and the postsynaptic architecture of PR synapses via
mechanisms that are disrupted in CSNB2. We will test this hypothesis with the following Aims: (1) Elucidate
the mechanism whereby Cav1.4 Ca2+ signals regulate the maturation and plasticity of synaptic ribbons (2) Define
the role of Cav1 Ca2+ signals in enabling the postsynaptic wiring of PR synapses (3) Determine the impact of
pathological variants of human Cav1.4 channels on PR synapse structure and function. The overall impact of our
research will be knowledge of: (a) the multi-faceted roles of Cav channels at a synapse that is crucial for vision,
and (b) how dysregulation specifically of Cav1.4 could lead to heterogeneous forms of vision impairment. More
broadly, our research is expected to provide insights into mechanisms that enable the proper synaptic
connectivity in the retina—a requirement for the successful restoration of vision through cell transplantation
therapies.

## Key facts

- **NIH application ID:** 10848381
- **Project number:** 5R01EY026817-08
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** AMY LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $476,484
- **Award type:** 5
- **Project period:** 2017-03-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848381

## Citation

> US National Institutes of Health, RePORTER application 10848381, Calcium channels in retinal photoreceptors (5R01EY026817-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848381. Licensed CC0.

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