Work

The Role of Retinal Antigen-Presenting Cells in Spontaneous Retinal Autoimmunity

Year: 2025

Type: article

Abstract: Purpose: We reported earlier that induction of spontaneous autoimmune uveoretinitis (SAU) correlated with the recruitment of circulating antigen-presenting cells (APCs) into the retina. Here, we investigated the role of resident retinal APCs on the course of SAU. Methods: R161H+/- mice (B10.RIII), which spontaneously and rapidly develop severe autoimmune uveoretinitis, were crossed with CD11cDTR/GFP mice (B6/J). R161H+/- mice on the B6/J background develop slower, less severe SAU than R161H+/--B10.RIII mice, allowing assessment of disease development relative to the depletion or activation of retinal or systemic APCs. The course of SAU was established in a cohort of control R161H+/- × CD11cDTR/GFP F1 mice and then reanalyzed in test cohorts following treatment with diphtheria toxin or stimulation by optic nerve crush (ONC) injury. Analysis was done by retinal imaging, flow cytometry, and histology. Results: Systemic depletion of APCs halted the progression of SAU in R161H+/- × CD11cDTR/GFP F1 mice and, if commenced early in the disease process, would reduce SAU severity. However, following depletion of APCs specifically from the retina, SAU in R161H+/- × CD11cDTR/GFP F1 mice progressed in a manner similar to that of control mice. In contrast, SAU in R161H+/- × CD11cDTR/GFP F1 mice was exacerbated following the activation of retinal APCs by ONC. Conclusions: Our observations that local depletion of retinal APCs failed to inhibit SAU progression and that depletion of circulating APCs not only limited SAU progression but also, under defined circumstances, reduced clinical SAU support the idea that circulating APCs are crucial for the induction and progression of SAU.

Source: Investigative Ophthalmology & Visual Science

DOI: 10.1167/iovs.66.11.26

Authors: Joe Sherman, Laura Burgstaler, Yunan Li, Heidi Roehrich, Dale S. Gregerson, Scott W. McPherson

Institution: University of Minnesota

Language: English

Topic: Ocular Diseases and Behçet’s Syndrome

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,850