title: In vivo multi-modal imaging of experimental autoimmune uveoretinitis in transgenic reporter mice reveals the dynamic nature of inflammatory changes during disease progression.
abstract: BACKGROUND
  Experimental 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.
  
  
  METHODS
  Transgenic 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. xiang.chen@monash.edu.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. jelena.kezic@monash.edu.
authors.forename: Jelena M
authors.initials: JM
authors.lastname: Kezic
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, Institute of Medical Science, Foresterhill, University of Aberdeen, Scotland, UK. j.forrester@abdn.ac.uk.|Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, Western Australia, Australia. j.forrester@abdn.ac.uk.|Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Crawley, Western Australia, Australia. j.forrester@abdn.ac.uk.
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. goldberg@wehi.edu.au.
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Goldberg
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. wicks@wehi.edu.au.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Wicks
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia. claude.bernard@monash.edu.
authors.forename: Claude C
authors.initials: CC
authors.lastname: Bernard
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. paul.mcmenamin@monash.edu.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases; D039521:CD11c Antigen / Q000235:genetics; D000073883:CX3C Chemokine Receptor 1; D004195:Disease Models, Animal; D018450:Disease Progression; D005136:Eye Proteins / Q000633:toxicity; D005620:Freund's Adjuvant / Q000633:toxicity; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064847:Multimodal Imaging; D009113:Muramidase / Q000235:genetics; D010446:Peptide Fragments / Q000633:toxicity; D019707:Receptors, Chemokine / Q000235:genetics; D012171:Retinal Vessels; D012173:Retinitis / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000473:pathology*; D012177:Retinol-Binding Proteins / Q000633:toxicity; D013997:Time Factors; D014605:Uveitis / Q000139:chemically induced / Q000150:complications* / Q000235:genetics* / Q000473:pathology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D039521:CD11c Antigen; D000073883:CX3C Chemokine Receptor 1; D005136:Eye Proteins; D005620:Freund's Adjuvant; D008164:Luminescent Proteins; D009113:Muramidase; D010446:Peptide Fragments; D019707:Receptors, Chemokine; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C471885:Cx3cr1 protein, mouse; C472450:lysozyme M, mouse