Uveitis in horses induced by interphotoreceptor retinoid-binding protein is similar to the spontaneous disease.
Abstract: Equine recurrent uveitis (ERU) is an inflammatory eye disease with high similarity to uveitis in man. It is the only spontaneous animal model for uveitis and the most frequent eye disease in horses affecting up to 10% of the population. To further investigate the pathophysiology of ERU we now report the establishment of an inducible uveitis model in horses. An ERU-like disease was elicited in seven out of seven horses by injection of interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. Control horses did not develop uveitis. The disease model is characterized by a highly reproducible disease course and recurrent episodes with an identical time course elicited in all horses by repeated IRBP injections. The histology revealed the formation of lymphoid follicle-like structures in the eyes and an intraocular infiltration dominated by CD3(+) lymphocytes, morphological patterns typical for the spontaneous disease. Antigen-specific T cell proliferation of PBL was monitored prior to clinical uveitis and during disease episodes. An initial T cell response to IRBP-derived peptides was followed by epitope spreading to S-antigen-derived peptides in response to subsequent immunizations. Thus, horse experimental uveitis represents a valuable disease model for comparative studies with the spontaneous disease and the investigation of immunomodulatory therapeutic approaches after onset of the disease.
Publication Date: 2002-09-11 PubMed ID: 12207344DOI: 10.1002/1521-4141(200209)32:93.0.CO;2-#Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article investigates the establishment of an induced uveitis model in horses to further understand the pathology of Equine recurrent uveitis (ERU), a common inflammatory eye disease in horses.
Research Purpose and Methodology
- The primary goal of the study was to create a reliable and reproducible disease model for uveitis in horses. This model would provide insights into the pathophysiology of ERU, a frequent eye condition found in up to 10% of horses, which bears high similarity to human uveitis.
- The researchers induced the ERU-like disease in seven horses by injecting them with interphotoreceptor retinoid-binding protein (IRBP) in complete Freund’s adjuvant, a substance used to boost immune response.
- The control group of horses, which did not receive the IRBP injections, did not develop uveitis, affirming the effectiveness of the induced uveitis model.
Findings and Characteristics of the Uveitis Model
- The induced ERU resulted in a highly reproducible disease course with recurrent episodes that occur at the same intervals in all horses, and these episodes were triggered by repeated IRBP injections.
- The histological examination of the eyes showed the development of lymphoid follicle-like structures and an intraocular infiltration primarily composed of CD3(+) lymphocytes, physical patterns typical for spontaneous ERU.
- The initial T-cell response to IRBP-derived peptides was observed. The study also observed ‘epitope spreading’ – a phenomenon where the immune response extends to structurally unrelated antigens following subsequent immunizations. In this case, the immune response extended to S-antigen-derived peptides.
Implications of the Disease Model
- The created model of induced uveitis in horses presents an important tool for research. It enables comparative studies between the induced and spontaneous disease, offering a greater understanding of the condition’s pathophysiology.
- With the model, researchers can investigate potential immunomodulatory therapeutic approaches after the onset of the disease, which can potentially lead to the development of effective treatments for ERU.
Cite This Article
APA
Deeg CA, Thurau SR, Gerhards H, Ehrenhofer M, Wildner G, Kaspers B.
(2002).
Uveitis in horses induced by interphotoreceptor retinoid-binding protein is similar to the spontaneous disease.
Eur J Immunol, 32(9), 2598-2606.
https://doi.org/10.1002/1521-4141(200209)32:93.0.CO;2-# Publication
Researcher Affiliations
- Institute for Animal Physiology, Ludwig-Maximilians-University, Munich, Germany. deeg@tiph.vetmed.uni-muenchen.de
MeSH Terms
- Amino Acid Sequence
- Animals
- Autoantigens / administration & dosage
- Autoantigens / immunology
- Autoantigens / toxicity
- Autoimmune Diseases / etiology
- Autoimmune Diseases / immunology
- Autoimmune Diseases / pathology
- Autoimmune Diseases / veterinary
- CD3 Complex / analysis
- Cattle
- Disease Models, Animal
- Eye Proteins
- Freund's Adjuvant
- Horse Diseases / etiology
- Horse Diseases / immunology
- Horse Diseases / pathology
- Horses
- Humans
- Immunization
- Immunization, Secondary
- Leukocytes, Mononuclear / drug effects
- Leukocytes, Mononuclear / immunology
- Lymphocyte Activation / drug effects
- Molecular Sequence Data
- Peptide Fragments / immunology
- Peptide Fragments / toxicity
- Pertussis Toxin / immunology
- Recurrence
- Reproducibility of Results
- Retinol-Binding Proteins / administration & dosage
- Retinol-Binding Proteins / immunology
- Retinol-Binding Proteins / toxicity
- Species Specificity
- T-Lymphocyte Subsets / immunology
- T-Lymphocyte Subsets / pathology
- Uveitis / etiology
- Uveitis / immunology
- Uveitis / pathology
- Uveitis / veterinary
Citations
This article has been cited 20 times.- Sprenzel CJ, Amann B, Deeg CA, Degroote RL. Glycan Signatures on Neutrophils in an Equine Model for Autoimmune Uveitis. Biomolecules 2025 Oct 12;15(10).
- Ahn M, Dostal J, Hegde P, Lee DJ. CTLA-4 expression on tregs is needed for suppression of autoimmune uveitis. Sci Rep 2025 May 22;15(1):17745.
- Degroote RL, Schmalen A, Hauck SM, Deeg CA. Unveiling Differential Responses of Granulocytes to Distinct Immunostimulants with Implications in Autoimmune Uveitis. Biomedicines 2023 Dec 20;12(1).
- Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro. Int J Mol Sci 2022 Aug 23;23(17).
- Fingerhut L, Yücel L, Strutzberg-Minder K, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N. Ex Vivo and In Vitro Analysis Identify a Detrimental Impact of Neutrophil Extracellular Traps on Eye Structures in Equine Recurrent Uveitis. Front Immunol 2022;13:830871.
- Wollanke B, Gerhards H, Ackermann K. Infectious Uveitis in Horses and New Insights in Its Leptospiral Biofilm-Related Pathogenesis. Microorganisms 2022 Feb 7;10(2).
- Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
- Wildner G, Diedrichs-Möhring M. Molecular Mimicry and Uveitis. Front Immunol 2020;11:580636.
- Wiedemann C, Amann B, Degroote RL, Witte T, Deeg CA. Aberrant Migratory Behavior of Immune Cells in Recurrent Autoimmune Uveitis in Horses. Front Cell Dev Biol 2020;8:101.
- Sharma J, Larkin J 3rd. Therapeutic Implication of SOCS1 Modulation in the Treatment of Autoimmunity and Cancer. Front Pharmacol 2019;10:324.
- Fischer BM, McMullen RJ Jr, Reese S, Brehm W. Intravitreal injection of low-dose gentamicin for the treatment of recurrent or persistent uveitis in horses: Preliminary results. BMC Vet Res 2019 Jan 16;15(1):29.
- Schauer M, Kleinwort KJH, Degroote RL, Wiedemann C, Kremmer E, Hauck SM, Deeg CA. Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity. Sci Rep 2018 Aug 17;8(1):12332.
- Sandmeyer LS, Bauer BS, Feng CX, Grahn BH. Equine recurrent uveitis in western Canadian prairie provinces: A retrospective study (2002-2015). Can Vet J 2017 Jul;58(7):717-722.
- Simeonova GP, Krastev SZ, Simeonov RS. Immunological and pathological investigations in equine experimental uveitis. Vet Res Commun 2016 Dec;40(3-4):107-115.
- Kielczewski JL, Horai R, Jittayasothorn Y, Chan CC, Caspi RR. Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function. J Immunol 2016 Feb 1;196(3):1013-25.
- Uhl PB, Amann B, Hauck SM, Deeg CA. Novel localization of peripherin 2, the photoreceptor-specific retinal degeneration slow protein, in retinal pigment epithelium. Int J Mol Sci 2015 Jan 26;16(2):2678-92.
- Degroote RL, Hauck SM, Amann B, Hirmer S, Ueffing M, Deeg CA. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis. PLoS One 2014;9(3):e91684.
- Kulbrock M, Lehner S, Metzger J, Ohnesorge B, Distl O. A genome-wide association study identifies risk loci to equine recurrent uveitis in German warmblood horses. PLoS One 2013;8(8):e71619.
- Verma A, Kumar P, Babb K, Timoney JF, Stevenson B. Cross-reactivity of antibodies against leptospiral recurrent uveitis-associated proteins A and B (LruA and LruB) with eye proteins. PLoS Negl Trop Dis 2010 Aug 3;4(8):e778.
- Verma A, Artiushin S, Matsunaga J, Haake DA, Timoney JF. LruA and LruB, novel lipoproteins of pathogenic Leptospira interrogans associated with equine recurrent uveitis. Infect Immun 2005 Nov;73(11):7259-66.
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