# T-cell mediated RGC damage in glaucoma

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $635,231

## Abstract

Abstract:
Primary open angle glaucoma (POAG) is a potentially blinding ocular disease that affects 60
million people world-wide. Reduction of IOP is currently the only glaucoma treatment, but fails to
preserve vision in a significant fraction of patients, suggesting that other –currently untreated-
factors contribute to the disease. Therefore, there is a critical need to identify these additional
pathomechanisms to aid the development of new therapeutic approaches that directly support
survival and function of retinal ganglion cells (RGC).
Our recently published studies have demonstrated that adoptive transfer of T-cells from
glaucomatous mice into normal recipients causes RGC loss in the recipients. We have also
demonstrated that the absence of T- and B-cells profoundly protects RGC in a mouse glaucoma
model. Preliminary data included in this application demonstrates that peripheral blood
mononuclear cells (PBMC) of glaucoma patients contain a higher fraction of CD4 cells
synthesizing TNFα and exhibit a higher activation state than those of controls. We further
demonstrate that glaucoma PBMC have a heightened propensity to damage RGC in an ex vivo
assay when compared to controls. Together, these findings strongly suggest that T-cell
mediated damage is one of the mechanisms contributing to RGC loss in both animal models
and in human patients.
This project is designed with the long-term goal to determine whether modulation of immune
responses provides vision saving benefits to glaucoma patients. The objective of this application
is to establish which subtype of CD4 T-cells mediates damage in the glaucoma retina and to
determine the functional significance of CD4 cell derived TNFα. To test our novel hypothesis we
will employ a transgenic mouse model of myocilin-associated spontaneous glaucoma that we
previously developed (Tg-MYOCY437H) containing an inducible Tnf knockout allele. We have also
developed a novel in vitro assay allowing the quantitation of the cytotoxic activity of patient
PBMC targeted toward RGC. Finally we propose to determine the activities T cells extravasated
in the glaucoma retina, as well as those in lymph nodes and PBMC by establishing detailed
gene transcription profiles.
Experimental proof that CD4 T-cell mediated mechanisms contribute to vision loss in patients
would establish new targets for the medical treatment of glaucoma. These in turn will pave a
way for future clinical studies with the ultimate aim of preserving the sight and improving the
quality of life of patients with primary open angle glaucoma.

## Key facts

- **NIH application ID:** 10773105
- **Project number:** 5R01EY034534-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** MARKUS H. KUEHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,231
- **Award type:** 5
- **Project period:** 2023-03-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773105

## Citation

> US National Institutes of Health, RePORTER application 10773105, T-cell mediated RGC damage in glaucoma (5R01EY034534-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10773105. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*