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The Role of Retinal Antigen-Presenting Cells in Spontaneous Retinal Autoimmunity
Joe Sherman1, Laura Burgstaler1, Yunan Li1
1Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States.
Investigative Ophthalmology & Visual Science
|August 11, 2025
Summary
Circulating antigen-presenting cells (APCs) are critical for spontaneous autoimmune uveoretinitis (SAU) development. Depleting systemic APCs halts SAU progression, while retinal APCs play a minor role.
Area of Science:
- Ophthalmology
- Immunology
- Autoimmunity
Background:
- Spontaneous autoimmune uveoretinitis (SAU) is linked to antigen-presenting cell (APC) recruitment into the retina.
- Investigating the role of resident retinal APCs is crucial for understanding SAU pathogenesis.
Purpose of the Study:
- To determine the role of resident retinal APCs in the course of spontaneous autoimmune uveoretinitis (SAU).
- To elucidate the contribution of circulating versus resident APCs in SAU development and progression.
Main Methods:
- Crossed R161H+/- mice with CD11cDTR/GFP mice to model SAU.
- Administered diphtheria toxin to deplete systemic APCs or used optic nerve crush (ONC) to activate retinal APCs.
- Analyzed SAU progression using retinal imaging, flow cytometry, and histology.
Main Results:
- Systemic APC depletion halted SAU progression and reduced severity when initiated early.
- Depletion of retinal APCs did not inhibit SAU progression.
- Activation of retinal APCs by ONC exacerbated SAU.
Conclusions:
- Circulating APCs are essential for the induction and progression of SAU.
- Resident retinal APCs play a less significant role in SAU progression compared to circulating APCs.
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