# New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $402,500

## Abstract

Abstract
 Autoimmune uveitis, a common cause of blindness, has an unknown etiology and no known cure. We
have been studying experimental autoimmune uveitis (EAU) induced in mice deficient in various complement
components, inhibitors, or receptors following active immunization with a retinal antigen and the adoptive transfer
of already primed retinal antigen-specific T cells. Our findings strongly suggest that complement, particularly the
complement receptors C3aR and C5aR, are required for not only the priming of autoreactive T cells in the
periphery, but also the migration and/or re-stimulation of already activated pathogenic T cells in the retina. These
findings suggest that these complement receptors could be new therapeutic targets for treating EAU and,
eventually, autoimmune uveitis.
 In this proposed work, we will focus on the previously unknown role of complement in regulating the
migration and/or re-stimulation of already primed autoreactive T cells in a target tissue, using EAU as a model.
We will also elucidate the underlying mechanisms using various systemic and cell-specific complement-related
gene knockout mice and other novel reagents. In addition, we will examine the efficacies and investigate the
underlying mechanisms of our novel complement-targeted reagents for suppressing the migration and re-
stimulation of previously activated uveitogenic T cells in the retina for the treatment of EAU both in mice and in
rats. These studies will significantly improve our understanding of the pathogenesis of autoimmune uveitis and
facilitate the development of novel complement-targeted therapeutics for the treatment of this blinding disease.

## Key facts

- **NIH application ID:** 10834908
- **Project number:** 5R01EY032458-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** FENG C LIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2021-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834908

## Citation

> US National Institutes of Health, RePORTER application 10834908, New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis (5R01EY032458-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834908. Licensed CC0.

---

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