In vivo multi-modal imaging of experimental autoimmune uveoretinitis in transgenic reporter mice reveals the dynamic nature of inflammatory changes during disease progression

Xiangting Chen, Jelena M Kezic, John V Forrester, Gabrielle L Goldberg, Ian P Wicks, Claude C Bernard, Paul G McMenamin

BackgroundExperimental autoimmune uveoretinitis (EAU) is a widely used experimental animal model of human endogenous posterior uveoretinitis. In the present study, we performed in vivo imaging of the retina in transgenic reporter mice to investigate dynamic changes in exogenous inflammatory cells and endogenous immune cells during the disease process.MethodsTransgenic mice (C57Bl/6 J Cx 3 cr1 GFP/+ , C57Bl/6 N CD11c-eYFP, and C57Bl/6 J LysM-eGFP) were used to visualize the dynamic changes of myeloid-derived cells, putative dendritic cells and neutrophils during EAU. Transgenic mice were monitored with multi-modal fundus imaging camera over five time points following disease induction with the retinal auto-antigen, interphotoreceptor retinoid binding protein (IRBP1¿20). Disease severity was quantified with both clinical and histopathological grading.ResultsIn the normal C57Bl/6 J Cx 3 cr1 GFP/+ mouse Cx3cr1-expressing microglia were evenly distributed in the retina. In C57Bl/6 N CD11c-eYFP mice clusters of CD11c-expressing cells were noted in the retina and in C57Bl/6 J LysM-eGFP mice very low numbers of LysM-expressing neutrophils were observed in the fundus. Following immunization with IRBP1¿20, fundus examination revealed accumulations of Cx3cr1-GFP+ myeloid cells, CD11c-eYFP+ cells and LysM-eGFP+ myelomonocytic cells around the optic nerve head and along retinal vessels as early as day 14 post-immunization. CD11c-eYFP+ cells appear to resolve marginally earlier (day 21 post-immunization) than Cx3cr1-GFP+ and LysM-eGFP+ cells. The clinical grading of EAU in transgenic mice correlated closely with histopathological grading.ConclusionsThese results illustrate that in vivo fundus imaging of transgenic reporter mice allows direct visualization of various exogenously and endogenously derived leukocyte types during EAU progression. This approach acts as a valuable adjunct to other methods of studying the clinical course of EAU.