# Regulation of the neuroinflammatory response in autoimmune uveitis

> **NIH NIH R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2024 · $425,000

## Abstract

Research Abstract: Autoimmune uveitis is a serious sight-threatening condition defined by an autoreactive
immune response against the retina and uveal tissues. In autoimmune uveitis, the retina and uveal tissues
become a target of autoreactive immune cells, which leads to irreversible neural damages and can progress to
significant visual impairment. Since the retina is a so-called “immune privileged” tissue protected by blood-
retinal barrier, how immune cells gain entry into the retina and what antigen presenting cell (APC) populations
are involved in local antigen presentation have been a long discussion. This proposal describes aims to
elucidate an innovative mechanism whereby retinal microglia mediate autoreactive immune cell entry into the
retina. Microglia are the resident immune cells of the central nervous system, including the retina, and function
in the homeostatic maintenance of the neuro-retinal microenvironment. The role and function of microglia in
disease progression is not well understood due to their multiple phenotypes and/or different stages of
activation that are associated with either harmful or beneficial effects in disease pathogenesis.
Our recent work demonstrated that microglial depletion inhibits development of EAU and that microglia are
essential to disease induction. Interestingly, retinal microglia are significantly activated in response to EAU
disease induction, quickly localizing to the retinal vasculature. However, our data indicated that microglia do
not function as APCs in disease initiation, but in fact function to facilitate infiltration of a variety of circulating
immune cells into the neuroretina. Our data highly suggested that microglia are key population that initiates
blood-retinal barrier breakdown and that the circulating APCs and T cells that enter the retina trigger the
subsequent vision altering auto-inflammatory response. However, the mechanisms by which this occurs
remains unknown.
In this proposal, we will elucidate the mechanism by which autoreactive immune cells gain entry into the retina
and how the subsequent autoimmune response develops during disease progression in a mouse model of
experimental autoimmune uveitis (EAU). We will begin by defining the initiating APC populations in EAU and
the contribution of microglial expression of MHC-II during EAU disease progression. Moreover, we will identify
the activation and kinetics of retinal microglia and infiltrating immune cells in EAU induction by using a single
cell RNA sequence profiling. Lastly, we will define the role of SIRPalpha/CD47, an immune axis that is highly
regulated in EAU and that functions in phagocytosis initiation and immune cell reactivity. Understanding the
mechanism by which microglia initiate autoimmune uveitis will likely open new avenues of therapy for this
disease as well as other blinding neovascular ophthalmic diseases.

## Key facts

- **NIH application ID:** 10744201
- **Project number:** 5R01EY031291-04
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** MEREDITH GREGORY-KSANDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $425,000
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744201

## Citation

> US National Institutes of Health, RePORTER application 10744201, Regulation of the neuroinflammatory response in autoimmune uveitis (5R01EY031291-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10744201. Licensed CC0.

---

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