Spontaneous Autoimmune Uveoretinitis Is Enhanced by Activation of Retinal Antigen Presenting Cells

Abstract

Purpose : We recently reported that induction of Spontaneous Autoimmune Uveoretinitis (SAU) is dependent on the recruitment of circulating antigen presenting cells (APC) into the retina (McPherson, et. al., J Neuroinflammation 19:295). However, whether retinal APC do enhance, limit, or remain neutral concerning the course of SAU remains to be studied. Here, we begin these investigations by asking whether activation of retinal APC can exacerbate SAU.

Methods : We created an R161H^+/- x CD11c^DTR/GFP F₁ mouse that develops SAU slower and with less severity than the original R161H line on the B10.RIII background (Horai, et. al., J Autoimmunity 44:21, provided by Dr. R. Caspi), providing a system more amenable for examining the cellular requirements and altering the course of SAU. R161H^+/- x CD11c^DTR/GFP F₁ mice were examined at 30 days of age for SAU and those free of any clinical signs of the disease by fundoscopic examination were given a given a unilateral (left eye, ipsilateral) optic nerve crush injury (ONC) to stimulate retinal APC. Eyes were examined by fundoscopy and harvested for histopathological analysis at 3 and 10 days post-ONC. Comparison of SAU was made between the ipsilateral and contralateral eyes of the ONC mice, and eyes from age matched R161H^+/- x CD11c^DTR/GFP F₁ mice not given an ONC. Additional analysis of retinal APC was done by flow cytometry.

Results : We observed a significant increase in the clinical and histological severity of SAU in the ipsilateral eyes of mice given an ONC compared to the contralateral eyes and eyes from age-matched mice without an ONC. The average clinical SAU score for ipsilateral eyes 3 days post-ONC was 1.10 versus 0.06 for the contra lateral eyes (ρ = 0.011) and 0.53 for non-ONC mouse eyes (ρ = 0.054). For 10-day post-ONC mice, the average clinical SAU score was 1.09 for ipsilateral eyes versus 0.50 (ρ = 0.0009) for the contralateral eyes and 0.59 (ρ = 0.0017) for non-ONC mouse eyes. Average histopathology scores for 10-day post-ONC mice were 0.79 for ipsilateral eyes versus 0.25 for contralateral eyes (ρ = 0.0006). In all cases there was no statistical difference in SAU scores between contralateral eyes and age-matched no-ONC eyes.

Conclusions : Although the induction of SAU is correlated with the recruitment of circulating APC into the retina, our results suggest that the activation state of retinal APC can influence the subsequent course of the disease.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.