Abstract
Purpose :
Uveitis is one of the sight-threatening diseases characterized by a heterogeneous group of intraocular inflammatory disorders. Recurrent uveal and other ocular tissue inflammation causes visual loss and ocular structural damages. Previous studies found that mineralocorticoid receptor (MR) is expressed in retinal tissues and that aldosterone (ALD), the ligand of MR, ameliorates ocular inflammation in an endotoxin-induced uveitis (EIU) model. In this study, we investigated the roles of MR in T cell-mediated autoimmune ocular inflammation in an experimental autoimmune uveitis (EAU) model.
Methods :
Female C57BL/6J wild-type mice aged 6–8 weeks, around 10g body weight per mouse, were induced with EAU by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptide 651-670. Mice were treated with dimethyl sulfoxide (DMSO, solvent control), 0.83µg ALD per mouse per day, or 20µg eplerenone per mouse per day (EPL, MR antagonist) by daily subcutaneous injection on days 1-23 after immunization (n=18 per group). On days 1, 7, 10, 14, 17, 21, and 23, EAU disease scores in live mice were evaluated by using confocal scanning laser ophthalmoscopy (cSLO) and fundus imaging. Fold change of retinal-choroidal thickness (RCT), compared to the baseline before EAU induction, was quantified based on the in vivo measurement by optical coherence tomography (OCT). Disease scores and RCT are expressed as mean+/-SD.
Results :
EAU mice treated with either DMSO, ALD or EPL showed no significant difference in EAU disease scores on days 0–17. On day 23, compared with mice treated with DMSO (EAU score 1.8+/-0.2 and RCT 1.07+/-0.02), mice treated with ALD had a lower disease score (1.0+/-0.2, p<0.05), decreased fold change of RCT (1.04+/-0.01, p<0.05), and attenuated retinal inflammatory characteristics in terms of optic nerve head inflammation, vitreous and retinal infiltrates, retinal edema, and vasculitis. In comparison to mice in DSMO group, mice treated with EPL showed a higher disease score (2.5+/-0.2, p<0.05), a higher fold change of RCT (1.09+/-0.01, p<0.05) and more severe retinal inflammatory characteristics on day 23.
Conclusions :
Our results indicate that MR is involved in autoimmune uveitis progression and that the activation of MR attenuates autoimmune ocular inflammation.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.