# Regulation of Calcium Signaling in Retinal Ganglion Cells after Nerve Injury

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2020 · —

## Abstract

Abstract
Severe reductions of vision and blindness due to ocular disease and trauma are major clinical problems that
have serious consequences on the Veteran's quality of life. Optic neuropathies from injury to the retina and
optic nerve are characterized by a loss of ganglion cells and their axons. Ganglion cell death is initiated by
excessive intracellular Ca2+ levels followed by a cascade of deleterious cellular processes that result in
apoptosis. Consistent with this observation is the enhancement of ganglion cell survival when reducing
intracellular Ca2+ levels with Ca2+ channel and calcium permeable AMPA receptor (CP-AMPAR) selective
blockers. The rationale underlying the proposed studies is that the reduction of ganglion cell intracellular Ca2+
levels is an important component of protective strategies for the treatment of ocular injury. Suppression of
elevated intracellular Ca2+ levels would provide a window for initiating ganglion cell survival and axonal
recovery therapies following injury.
Proposed studies will test the hypothesis that suppression of elevated intracellular Ca2+ after optic nerve
trauma enhances ganglion cell survival.
Specific Aim 1 will determine the contributions of L-type Ca2+ channels and CP-AMPARs to ganglion
cell Ca2+ levels following optic nerve injury. Investigations will determine A) the transcriptional and
translational regulation of L-type Ca2+ channels, CP-AMPARs and the RNA-specific editing enzyme, ADAR2,
and B) characterize the physiological and biophysical properties of the L-type Ca2+ channels and CP-AMPARs.
Specific Aim 2 will test the hypothesis that pharmacological antagonism or genetic suppression by
siRNA of L-type Ca2+ channels stabilizes ganglion cell Ca2+ levels and enhances ganglion cell survival
after optic nerve injury. Investigations will test A) the action of the Ca2+ channel antagonist lomerizine on the
expression and function of L-type Ca2+ channels, B) if siRNA-mediated reduction of L-type Ca2+ channel
subunit expression decreases ganglion cell intracellular Ca2+ levels and C) whether these treatments enhance
ganglion cell survival following optic nerve injury.
Specific Aim 3 will test the hypothesis that pharmacological antagonism of AMPARs or genetic
regulation of the AMPAR subunit, GluA2, the auxiliary subunit, GSG1L, or the editing enzyme, ADAR2,
stabilizes ganglion cell intracellular Ca2+ levels, and enhances ganglion cell survival after optic nerve
injury. Investigations will test if A) the CP-AMPAR blockers, philanthotoxin-433 and 1-naphthyl acetyl
spermine and B) the siRNA-mediated reduction of GSG1L, which regulates GluA2 (edited and unedited)
subunits and CP-AMPA expression, reduces ganglion cell Ca2+ permeability and intracellular Ca2+ levels; C) if
GluA2(R) (edited) subunit or ADAR2 gene expression reduces ganglion cell Ca2+ permeability and intracellular
Ca2+ levels and D) these pharmacological and genetic approaches enhance ganglion cell survival following
optic nerve injury...

## Key facts

- **NIH application ID:** 9864010
- **Project number:** 5I01BX000764-08
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** NICHOLAS C. BRECHA
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2011-07-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864010

## Citation

> US National Institutes of Health, RePORTER application 9864010, Regulation of Calcium Signaling in Retinal Ganglion Cells after Nerve Injury (5I01BX000764-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864010. Licensed CC0.

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