# Bioassay to Predict the Development and Progression of Glaucoma

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2020 · —

## Abstract

Glaucoma is one of the most common causes of irreversible vision loss and blindness world wide. The disease
affects a large number of veterans and degrades their quality of life. Loss of vision is ultimately due to the
degeneration of retinal ganglion cells (RGC) which are required to convey visual information from the retinal
photoreceptors to the visual centers of the brain. It is currently unclear what initially causes the damage to
RGC.
 It has been well established that the degeneration of the RGC is accompanied by retinal neuroinflammation
characterized by microglial activation, expression of proinflammatory molecules, upregulation of MHC II
molecules, and retinal synthesis of components of the complement cascade. Preliminary data included in this
application demonstrate that glaucomatous RGC degeneration also elicits a cellular autoimmune response in
mouse models of the disease. Adoptive transfer of splenocytes or T cells, but not B cells, from glaucomatous
mice into healthy, normotensive recipients elicits slow and progressive loss of RGC. Other cell types of the
retina do not appear to be affected. Importantly, we further demonstrate that transfer of immune cells from
human glaucoma patients into immune deficient mice also leads to specific RGC loss in the recipient mice.
This was invariably the case when material from patients with disc hemorrhages (a clinical sign of ongoing
glaucomatous degeneration) was used. Material from patients with glaucoma, but without a disk hemorrhage,
causes RGC loss in mice to a varying degree. Transfer of cells from healthy controls causes no damage.
We hypothesize that the amount of RGC loss in the mouse is correlated to the vision loss that will be
experienced by the donating patient in the coming months. Thus, transfer of immune cells from human patients
to the mouse is a predictor of future damage and can serve to identify those patients who would benefit from
aggressive clinical interventions. Early and maximal treatment could serve to prevent loss of vision and decline
of quality of life in affected veterans. This proposal will test this hypothesis by obtaining blood derived immune
cells from veterans with primary open angle glaucoma. These cells will be transferred to the mice, and the
resulting damage will be quantitated. Patients will be re-examined after two years and the degree of vision loss
and decline of quality of life will be correlated to RGC loss in the mouse model. Additional experiments are
proposed to further define the type of immune cell mediating this phenomenon. Finally we will determine if
immune modulation in the recipient mouse can prevent RGC loss. If successful these data might point out new
approaches to prevent progressive vision loss in glaucoma patients.
The concept of a T cell based autoimmune response associated with vision loss in glaucoma is very innovative
and has potentially significant clinical ramifications. The development of a predictive assay based upon this
res...

## Key facts

- **NIH application ID:** 9971361
- **Project number:** 5I01RX002860-03
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** MARKUS H. KUEHN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971361

## Citation

> US National Institutes of Health, RePORTER application 9971361, Bioassay to Predict the Development and Progression of Glaucoma (5I01RX002860-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971361. Licensed CC0.

---

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