Abstract

Acute anterior uveitis (AAU) is the most common form of intraocular inflammation of unknown etiology and is a major cause of visual disability in our society. 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. Experimental autoimmune anterior uveitis (EAAU)is an organ specific autoimmune disease of the eye, which resembles AAU. It is produced in the Lewis rat by an antigen specific CD4+ T cell response to melanin-associated antigen (MAA) derived from bovine iris and ciliary body. We have recently purified the pathogenic antigen to homogeneity and our results suggest that it is a 22 kD fragment of Type I collagen, alpha-2 chain. The pathogenic antigen is tissue specific, being localized solely to the eye.
The specific aims of our proposal are: A. Determine the primary structure of MAA; B. Identify the immunogenic and pathogenic epitopes of MAA; C. Modify the course of EAAU. The opportunity to study a clinically relevant animal model of AAU may allow the identification of treatment modalities which may prevent the occurrence of AAU rather than solely allow treatment of the acute episode, which is the current state of the art.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010543-07
Application #
6179857
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1994-04-01
Project End
2001-01-31
Budget Start
2000-04-01
Budget End
2001-01-31
Support Year
7
Fiscal Year
2000
Total Cost
$195,677
Indirect Cost

  Institution

Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

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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