# Resolution of ocular inflammation: the role of type 1 conventional dendritic cells

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2022 · $218,240

## Abstract

Project Summary
Non-infectious uveitis is comprised of a heterogeneous group of clinically-defined diseases for which empiric
therapy fails many patients. Molecular characterization of uveitis, on the other hand, would result in more
precise classification of disease subtypes, while simultaneously providing pathophysiologic insight with
therapeutic potential. This could spare patients unnecessary toxic side effects or loss of vision due to
therapeutic inefficacy. Consequently, there is a critical need to better classify uveitis subtypes in order to
discover more effective strategies for targeted immune suppression. The long-term goal is to develop a
platform for molecular characterization of uveitis that will eventually facilitate precision medicine treatment
strategies. The approach is to utilize validated experimental techniques to explore novel observations obtained
from single cell RNA-Sequencing (scRNA-Seq), a high-definition gene expression analysis of ocular immune
cells. Specifically, the central hypothesis for this proposal, that type 1 conventional dendritic cells (DC1s)
promote the resolution of ocular inflammation, is based on primary observations of human ocular DC1s
obtained via scRNA-Seq. The overall objectives of this proposal are to a) ascertain the role of DC1s in ocular
inflammation, and b) to determine how patient-specific alterations in DC1s contribute to the chronicity of
uveitis. Toward these ends, the following specific aims will be pursued: 1) Test the hypothesis that the ocular
microenvironment promotes pro-resolution DC1s. 2) Test the hypothesis that DC1s promote the resolution of
ocular inflammation. 3) Test the hypothesis that patient-specific DC1 gene expression signatures predict
uveitis chronicity. In aim 1, the effect of the ocular microenvironment on DC1s will be tested by a) analyzing
aqueous-exposed human DC1s in vitro and b) analyzing murine DC1s in 2 distinct models of ocular
inflammation in vivo. In aim 2, the specific effects of DC1s on disease chronicity during ocular inflammation will
be explored using mice deficient in DC1s. Finally, in aim 3, the transcriptional signatures that best predict
chronic and acute uveitis will be validated and used to a) identify peripheral blood biomarkers and b) identify
potential therapeutic targets. This contribution will be significant because it will improve our ability to define
uveitis entities based on pathophysiologic mechanisms that can then be appropriately targeted by precision
application of immune therapies. This proposal is innovative in the use of scRNA-Seq to generate testable
hypotheses from in-depth analysis of patient samples. Ultimately, improved molecular characterization of
uveitis based on identification and validation of differential gene expression provides a scaffold for future
analyses that will facilitate a precision medicine approach to immune therapy.

## Key facts

- **NIH application ID:** 10449898
- **Project number:** 1K08EY033045-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lynn M Hassman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $218,240
- **Award type:** 1
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449898

## Citation

> US National Institutes of Health, RePORTER application 10449898, Resolution of ocular inflammation: the role of type 1 conventional dendritic cells (1K08EY033045-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10449898. Licensed CC0.

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