# Immune Responses in Neuronal Cell Death

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2020 · —

## Abstract

Retinal ganglion cells (RGCs) are the only output neurons that relay visual signals from the eyes to the brain.
RGC death is a crucial element in the pathogenesis in many retinal diseases leading to blindness, such as
glaucoma and optic nerve injury. These diseases are also the leading causes of blindness of veterans. The
prevalence of blinding diseases in veterans is very high and about 20.5-63.4% of veterans were diagnosed with
at least one ocular disease. A significant cause of vision defects of VA patients is traumatic optic neuropathy
(TON) related to traumatic brain injury (TBI). TBI is a significant cause of death and disability worldwide, and it
is estimated 1.6-3.8 million new TBI cases occur in the US each year. About 57-66% veterans with TBI had
vision problems and no treatment for TON is more effective than observation. Therefore, the treatment of vision
impairment related to TBI is a significant challenge for the VA healthcare system, and it has been limited by
incomplete understanding of the molecular mechanisms that mediating the RGC death in these diseases. In
addition to the primary injury, secondary injuries dramatically worsen the damage and cause about 40% of TBI
deaths. One of the significant secondary injuries of TBI and TON is glutamate excitotoxicity, the pathological
process by which neurons are damaged and eventually killed by excessive stimulation of glutamate receptors.
This process also plays critical roles in other neurodegenerative diseases, such as glaucoma, which specifically
injure RGCs. Therefore, effectively minimizing or preventing glutamate excitotoxicity is crucial to reduce RGCs
death and preserve vision. Based on the understanding of the mechanisms which control the vulnerability of
RGCs, we plan to develop novel treatment strategies to prevent RGC death in these diseases.
 Recent studies have shown that immune molecules play essential roles in neuron repair and cell death in
CNS diseases. In the retina, the receptors of major histocompatibility complex (MHC) class I molecules, T-cell
receptor, (TCR) and their associated proteins are expressed by RGCs. The mutation of these molecules reduced
the susceptibility of RGCs to glutamate excitotoxicity and optic nerve crush (ONC). These findings strongly
support the possibility that MHCI/TCR could protect RGCs from death. Also, the susceptibility of RGCs to
glutamate excitotoxicity and ONC vary significantly among different types of RGC and the types of pathological
insults. These results demonstrate that multiple mechanisms regulate the death of RGCs and, therefore, the
treatment strategies to prevent RGC death in diseases need to be designed accordingly.
 In this study, we plan to conduct proof-of-principle studies to establish the role of MHCI-TCR as a critical
mediator of neuronal injury induced by glutamate excitotoxicity and ONC. Our preliminary results showed that
susceptibility of RGCs to NMDA excitotoxicity and ONC is RGC type-dependent, mutation of CD3z...

## Key facts

- **NIH application ID:** 9890450
- **Project number:** 2I01BX002412-05A1
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Ning Tian
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2015-10-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890450

## Citation

> US National Institutes of Health, RePORTER application 9890450, Immune Responses in Neuronal Cell Death (2I01BX002412-05A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890450. Licensed CC0.

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