The most frequent form of human intraocular inflammation is acute anterior uveitis (AAU) of unknown etiology. The recurrent nature of the disease can lead to permanent visual loss from the secondary complications of cystoid macular edema, posterior subcapsular cataract or glaucoma. Consequently, it is a major cause of visual disability in our society. Until recently, no experimental animal model of AAU existed. In the most widely studied model of autoimmune intraocular inflammation, experimental autoimmune uveitis (EAU) to various soluble retinal proteins, the retina and choroid are the foci of inflammation not the iris/ciliary body (CB) as in human AAU. We, as well as Brockhuyse and colleagues, have described a new experimental model in the Lewis rat which is induced by immunization with a bovine melanin associated protein derived from the iris/CB and which mimics human AAU. We refer to it as experimental acute anterior uveitis (BAAU). The studies in this proposal are designed to complete the immunologic characterization of the autoimmune model, to identify the pathogenic protein and its immunodominant epitopes, to explore the immunopathogenesis of the disease and to study the efficacy of various treatment approaches. The opportunity to directly study a clinically relevant model of intraocular inflammation is exciting and provides unique possibilities to understand and prevent a disease which is associated with significant morbidity and which can only be treated symptomatically, but not cured.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010543-05
Application #
2684561
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1994-04-01
Project End
1999-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Bora, Nalini S; Sohn, Jeong-Hyeon; Bora, Puran S et al. (2005) Anti-inflammatory effects of specific cyclooxygenase 2,5-lipoxygenase, and inducible nitric oxide synthase inhibitors on experimental autoimmune anterior uveitis (EAAU). Ocul Immunol Inflamm 13:183-9
Bora, Nalini S; Sohn, Jeong-Hyeon; Kang, Shin-Goo et al. (2004) Type I collagen is the autoantigen in experimental autoimmune anterior uveitis. J Immunol 172:7086-94
Sohn, Jeong-Hyeon; Bora, Puran S; Suk, Hye-Jung et al. (2003) Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat Med 9:206-12
Sohn, J H; Kaplan, H J; Suk, H J et al. (2000) Complement regulatory activity of normal human intraocular fluid is mediated by MCP, DAF, and CD59. Invest Ophthalmol Vis Sci 41:4195-202
Sohn, J H; Kaplan, H J; Suk, H J et al. (2000) Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins. Invest Ophthalmol Vis Sci 41:3492-502
Woon, M D; Kaplan, H J; Bora, N S (1998) Kinetics of cytokine production in experimental autoimmune anterior uveitis (EAAU). Curr Eye Res 17:955-61
Bora, N S; Woon, M D; Tandhasetti, M T et al. (1997) Induction of experimental autoimmune anterior uveitis by a self-antigen: melanin complex without adjuvant. Invest Ophthalmol Vis Sci 38:2171-5
Simpson, S C; Kaplan, H J; Bora, N S (1997) Uveitogenic proteins isolated from bovine iris and ciliary body. Eye (Lond) 11 ( Pt 2):206-8
Bora, N S; Bora, P S; Tandhasetti, M T et al. (1996) Molecular cloning, sequencing, and expression of the 36 kDa protein present in pars planitis. Sequence homology with yeast nucleopore complex protein. Invest Ophthalmol Vis Sci 37:1877-83
Bora, N S; Bora, P S; Kaplan, H J (1996) Identification, quantitation, and purification of a 36 kDa circulating protein associated with active pars planitis. Invest Ophthalmol Vis Sci 37:1870-6

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