# CALCIUM HOMEOSTASIS IN MAMMALIAN ROD AND CONE PHOTORECEPTORS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $184,022

## Abstract

ABSTRACT
Calcium (Ca2+) is a ubiquitous signaling molecule that controls the function and survival
of neurons. The disrupted Ca2+ homeostasis in a wide range of photoreceptor mutations
is believed to cause cell death, retinal degeneration and blindness. In vertebrate
photoreceptors, Ca2+ changes also modulate the shutoff of the phototransduction
cascade to accelerate light response recovery and background adaptation. It is thought
that the concentration of Ca2+ in the outer segments of vertebrate photoreceptors is
controlled by a dynamic balance between influx via the cGMP-gated (CNG) channels
and extrusion via cell-specific Na+/Ca2+, K+ exchangers (NCKX), NCKX1 in rods and
NCKX2 in cones. However, the extent to which these exchangers control the Ca2+
homeostasis in mammalian photoreceptors and modulate phototransduction and cell
survival has not been determined. In addition, it is not known whether other active or
passive mechanisms for extruding Ca2+ are at play in the outer segments of mammalian
rods and cones. We will perform experiments to establish the role of CNG and NCKX1 in
regulating the Ca2+ homeostasis in mammalian rods and their effect on long-term rod
survival and degeneration. We will also test the hypothesis that abnormal photoreceptor
Ca2+ homeostasis mediates photoreceptor degeneration in a variety of blinding diseases
and will determine the therapeutic potential of restoring the Ca2+ flux balance in
photoreceptor channelopathies. We have identified NCKX4 as a second Na+/Ca2+, K+
exchanger expressed in mammalian cones. We will perform experiments to analyze the
expression profile, morphology, and functional properties of NCKX2- and NCKX4-
deficient mouse cones. These experiments will establish the molecular mechanisms for
the efficient extrusion of Ca2+ from mammalian cone photoreceptors critical for the fast
response kinetics and background adaptation of cones as our daytime photoreceptors
as well as their effect on cone long-term survival and degeneration. Collectively, our
experiments will establish the molecular mechanisms that mediate the extrusion of Ca2+
from mammalian photoreceptors. They will also help us understand the link between
abnormal Ca2+ homeostasis and photoreceptor degeneration and might potentially lead
to the development of treatments for channelopaties.

## Key facts

- **NIH application ID:** 10403734
- **Project number:** 7R01EY027387-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Jeannie Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,022
- **Award type:** 7
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403734

## Citation

> US National Institutes of Health, RePORTER application 10403734, CALCIUM HOMEOSTASIS IN MAMMALIAN ROD AND CONE PHOTORECEPTORS (7R01EY027387-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10403734. Licensed CC0.

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