# Antigen presentation to the adaptive immune system in the choroid contributes to ocular autoimmune disease

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2024 · $240,262

## Abstract

Project summary:
The overarching goal of this project is to develop the principal investigator (PI) into an independent clinician-
scientist contributing to the field of ocular autoimmunity. The PI has obtained his PhD in neuroscience, exploring
the roles of the adaptive immune system in axonal injury models. He has additional clinical training in
ophthalmology and subspecialty training in uveitis and ocular immunology, which forms the basis for his medical
practice in the Department of Ophthalmology and Visual Sciences at Washington University in St. Louis. The
five-year career development plan outlined here will utilize a combination of didactic courses, individualized
training from expert collaborators, and mentorship from established investigators to enhance his knowledge
base, to learn new experimental models he can continue to use in his career, and to define the research
questions on which he will base the start of his independent research program. By the end of this program, he
will have acquired the skills necessary to become an independent investigator.
His primary mentor is Rajendra Apte, MD PhD, an R01-funded investigator who has a longitudinal track record
of training early-stage investigators that have gone on to productive independent careers. He is a preeminent
scholar in the field of choroidal immunity and has a strong background as a clinician scientist that will be vital for
helping the PI navigate the challenges involved in transitioning to an independent lab. Dr. Apte will be supported
by Rachel Caspi, PhD, the world-leading expert in experimental autoimmune uveitis, Jonathan Kipnis, PhD, the
foremost expert in the adaptive immune system in border tissues, and Gregory Wu, MD PhD, a recent K08
awardee and expert on CNS autoimmunity. The PI will take advantage of his mentorship committee and the
vibrant scientific environment of Washington University, one of the world’s premiere medical research
institutions, to develop the unexplored topic of the adaptive immune response in the choroid.
Uveitis is one of the leading causes of preventable blindness, and while much work has gone in to evaluating
the effects of T cell-derived cytokines, there is a significant gap in understanding of the anatomy of the immune
response including where the adaptive immune system interfaces with ocular antigens. This deficit has led to
toxic and often ineffective systemic therapies as the mainstay of treatment. We show that intraocular antigens
are taken up in the choroid, a tissue that has a rich adaptive immune presence. In autoimmune uveitis there is
an increase of CD4+ T cells in the choroid, indicating that the choroid plays a vital role as the immune interface
between the intraocular space and adaptive immune system. In this proposal, we will test the hypothesis that
the adaptive immune system is activated by retinal antigens in the choroid and that this interaction plays a central
role in uveitis. We will further elucidate the mechanisms contr...

## Key facts

- **NIH application ID:** 10911300
- **Project number:** 5K08EY034601-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** James Walsh
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $240,262
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911300

## Citation

> US National Institutes of Health, RePORTER application 10911300, Antigen presentation to the adaptive immune system in the choroid contributes to ocular autoimmune disease (5K08EY034601-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10911300. Licensed CC0.

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