title: Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats.
abstract: OBJECTIVE
  The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats.
  
  
  METHODS
  In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays.
  
  
  RESULTS
  Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU.
  
  
  CONCLUSIONS
  Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and vitreous of both models and may be a viable therapeutic target.
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Pepple
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Rotkis
authors.affiliation: Alcon Research Laboratories, Fort Worth, Texas, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Van Grol
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Leslie
authors.initials: L
authors.lastname: Wilson
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Sandt
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Lam
authors.affiliation: Alcon Research Laboratories, Fort Worth, Texas, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Carlson
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington, United States 3Department of Biological Structure, University of Washington, Seattle, Washington, United States 4Department of Pathology, University of Washington, Seattle, Washin.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Van Gelder
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005260:Female; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*
chemical_list: D016207:Cytokines