# Immune Privilege, Müller cells, and Autophagy

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $411,102

## Abstract

Abstract
 Immune privilege is a term applied to organs such as the eye that have a unique relationship with the
immune response. These sites prohibit the spread of inflammation since even minor episodes can threaten
vision. The breakdown of immune privilege is thought to have serious consequences for the eye; however, in
spite its powerful influence on inflammation we know little about how immune privilege influences retinal
diseases. Müller cells are the major glial cell of the retina that maintain structural integrity. They react in
virtually every eye disease but are strikingly resistant damage; importantly they can suppress inflammation.
Based on this they should be key participants in immune privilege, but this is not understood. The biological
process of autophagy (literally self-eating) is a recycling system that destroys inflammation-inducing cellular
debris to prevent tissue damage. Because immune privilege, Müller cells, and autophagy all have anti-
inflammatory properties, we will test the novel hypothesis that Müller glial cells utilize the autophagy pathway to
support the anti-inflammatory nature of the eye (i.e. immune privilege). We will do this by examining
intraocular inflammation in 2 well-characterized disease models, endotoxin induced uveitis (EIU) and
experimental autoimmune uveitis (EAU), utilizing mice with autophagy-deficient retinal Müller cells. Since EIU
is mediated by the innate arm of the immune system and EAU is an antigen specific T cell mediated disease
we will get thorough understanding as to how Müller cell autophagy influences different types of immune
mediated diseases of the eye. In Aim 1 we will assess the intraocular inflammatory response in these models
by comparing control mice with mice that have had the essential autophagy genes Atg5 and Fip200 deleted
specifically in Müller glial cells. We will evaluate inflammatory infiltrates, cytokine production, and retinal
integrity in both models. Preliminary data suggests that inflammation and retinal damage are enhanced in the
presence of autophagy deficient Müller cells in both models. In Aim 2 we will we will define the molecular basis
of these enhanced inflammatory response to determine the contribution of autophagy to immunoregulatory
properties of Müller cells in the eye. Studies will include scRNA-seq analysis, examination of the blood retinal
barrier, analysis of the T-cell response in EAU, and morphological analysis. In Aim 3 we will test the idea that
autophagy supports phagocytosis in Müller cells promoting their anti-inflammatory properties using the process
of LC3-associated phagocytosis (or LAP). We will test whether LAP recovers a portion of the vitamin A for the
Müller visual cycle. By elucidating the role of Müller cells and autophagy in immune privilege we will better
understand their influence on ocular inflammatory responses. Thus, rather than just treating inflammation, we
could consider upregulating immune privilege alone, or in combination ...

## Key facts

- **NIH application ID:** 10872176
- **Project number:** 5R01EY034160-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Thomas Almon Ferguson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,102
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872176

## Citation

> US National Institutes of Health, RePORTER application 10872176, Immune Privilege, Müller cells, and Autophagy (5R01EY034160-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10872176. Licensed CC0.

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