# Manipulation of Immuity to Treat Uveitis

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $400,125

## Abstract

The goal of this proposal is to further understand how the neuropeptide alpha-melanocyte stimulating hormone
(α-MSH) regulates immunity, and how it can be used to suppress uveitis to reestablish immune privilege.
Previously published work, and the progress of our past grant-period demonstrated that α-MSH-treatment
during uveitis can restore immunosuppressive activity of retinal pigment epithelial cells (RPE). In addition, we
have demonstrated that part of immune privilege is suppression of the phagocytic/antigen-processing pathway
within macrophages by healthy RPE. This suppression is mediated by α-MSH produced by RPE and is
dependent on expression of the α-MSH-receptor, melanocortin 5 receptor (MC5r), in the retina. Therefore,
suppression of EAU, and the induction of regulatory T cells by α-MSH-therapy is possibly associated with
regulating antigen presenting cell activity within the uveitic eye. This would be mediated through α-MSH
binding specific melanocortin-receptors on the RPE and APC of the retina. Therefore, we hypothesize that α-
MSH regulates the processing and presentation of antigen within the immune privileged microenvironment,
and that α-MSH-therapy acts through this mechanism to suppress autoimmune uveitis. We will demonstrate
this regulation by assessing the role of α-MSH to regulate the phagocytic pathway in macrophages and
microglial cells; by determining the ability of α-MSH-treated APC to antigen-activate effector T cells; and
assess the potential for α-MSH to mediate innate-immune memory tolerance in macrophages. The α-MSH-
therapy will involve treating EAU with whole neuropeptide and specific melanocortin-receptor-agonists. The
regulation of antigen uptake, processing, and presentation will be assayed on both tissue macrophages, and
retinal microglial cells. Also, we will examine retinal microglial cells and α-MSH-treated macrophages for
expression of markers and activity associated with innate-immune memory tolerance. We will examine
changes in this regulation in the initial stages of EAU as suggested by our preliminary data. Our proposed work
will have a meaningful impact, because the results will provide new information about the molecular
mechanisms of uveitis, and α-MSH anti-inflammatory-activity. Also, it will define how melanocortin-based
therapy can regulate antigen presentation and T cell activation by suppressing the central drivers of
autoimmune disease.

## Key facts

- **NIH application ID:** 10115041
- **Project number:** 5R01EY025961-06
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Andrew W Taylor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,125
- **Award type:** 5
- **Project period:** 2016-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115041

## Citation

> US National Institutes of Health, RePORTER application 10115041, Manipulation of Immuity to Treat Uveitis (5R01EY025961-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115041. Licensed CC0.

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