PMID- 26747775
OWN - NLM
STAT- MEDLINE
DCOM- 20160331
LR  - 20230717
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 56
IP  - 13
DP  - 2015 Dec
TI  - Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a 
      Model of Uveitis in Rats.
PG  - 8438-48
LID - 10.1167/iovs.15-17523 [doi]
AB  - PURPOSE: 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-1beta, 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-1alpha (MIP-1alpha), and IL-17A. In 
      the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1alpha 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.
FAU - Pepple, Kathryn L
AU  - Pepple KL
AD  - Department of Ophthalmology, University of Washington, Seattle, Washington, 
      United States.
FAU - Rotkis, Lauren
AU  - Rotkis L
AD  - Department of Ophthalmology, University of Washington, Seattle, Washington, 
      United States.
FAU - Van Grol, Jennifer
AU  - Van Grol J
AD  - Alcon Research Laboratories, Fort Worth, Texas, United States.
FAU - Wilson, Leslie
AU  - Wilson L
AD  - Department of Ophthalmology, University of Washington, Seattle, Washington, 
      United States.
FAU - Sandt, Angela
AU  - Sandt A
AD  - Department of Ophthalmology, University of Washington, Seattle, Washington, 
      United States.
FAU - Lam, Deborah L
AU  - Lam DL
AD  - Department of Ophthalmology, University of Washington, Seattle, Washington, 
      United States.
FAU - Carlson, Eric
AU  - Carlson E
AD  - Alcon Research Laboratories, Fort Worth, Texas, United States.
FAU - Van Gelder, Russell N
AU  - Van Gelder RN
AD  - 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.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - K08 EY023998/EY/NEI NIH HHS/United States
GR  - P30 EY001730/EY/NEI NIH HHS/United States
GR  - K08EY023998/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Eye Infections, Bacterial/metabolism/microbiology/*pathology
MH  - Female
MH  - Mycobacterium tuberculosis/*isolation & purification
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Uveitis/metabolism/microbiology/*pathology
PMC - PMC4699411
EDAT- 2016/01/10 06:00
MHDA- 2016/04/01 06:00
PMCR- 2016/06/01
CRDT- 2016/01/10 06:00
PHST- 2016/01/10 06:00 [entrez]
PHST- 2016/01/10 06:00 [pubmed]
PHST- 2016/04/01 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 2480575 [pii]
AID - Customer No. IOVS-15-17523 [pii]
AID - 10.1167/iovs.15-17523 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8438-48. doi: 10.1167/iovs.15-17523.