Immunopathology of recurrent uveitis in spontaneously diseased horses.
Abstract: Equine recurrent uveitis (ERU) is the most serious eye disease in horses worldwide. Despite the fact that ERU is generally considered to be immune mediated, a detailed description of the histopathology of the posterior part of ERU eyes is lacking. Here, we examined sections of paraffin-embedded eyes using histological and immunhistological methods. Twenty seven eyes of 20 horses with ERU and 30 eyes of 15 healthy control horses were included in this study. We could consistently demonstrate an involvement of the retina and the choroid in all examined eyes of horses with spontaneous ERU. In eyes with minimal histopathological changes, the infiltrates consisted almost exclusively of T-cells. Histopathological changes start with the destruction of the photoreceptor outer segments, which often leads to focal retinal detachment. In more severely affected eyes, there is additional disintegration of the ganglion cell layer and the inner nuclear layer. In almost all examined eyes, lymphoid follicle formation could be demonstrated. Typical localizations of these follicles were the iris stroma and the choroid underneath the transition zone of the retina without photoreceptor cells to the region containing photoreceptor cells. These follicles consist of a T-cell rich periphery with a small center of CD3-negative lymphocytes. In cases with extreme histopathological changes, the retinal architecture is widely disintegrated with massive infiltration of the retina, the choroid, and the ciliary body by several types of inflammatory cells. Necrotic remnants of the retina are end-stage findings and there is only a minor inflammatory infiltration left. This study provides clear evidence that the retina is involved in all stages of ERU. Inflammation is mainly driven by T-cells as T-cells were demonstrated in mild stages of the disease and are also the predominating cell type in all other stages of ERU.
Publication Date: 2002-07-26 PubMed ID: 12137758DOI: 10.1006/exer.2002.2011Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on the study of ocular diseases in horses, particularly Equine Recurrent Uveitis (ERU), an immune-mediated eye disease. In this study, the researchers examined the eyes of both diseased and healthy horses to fully understand the effects and progression of ERU.
Research Methodology
- The researchers performed a detailed histological and immunohistological examination of paraffin-embedded eyes from 20 horses with ERU, and compared the results with those from 15 healthy control horses.
- The main focus was to understand the effects of ERU on the retina and the choroid of the eye, as these are the segments most affected by the disease.
Findings
- The results consistently showed retinal and choroidal involvement in the instances of ERU in horses.
- In the early stages with minimal histopathological changes, it was observed that the infiltrates within the eye were almost exclusively T-cells.
- The disease starts by destroying the outer segments of the photoreceptors, leading to focal retinal detachment. As the severity of ERU increases, there’s disintegration of the ganglion cell layer and the inner nuclear layer.
- Lymphoid follicle formation was observed in the majority of the examined eyes. These follicles are typically found in the iris stroma and the choroid, and contain a high concentration of T-cells with a center of CD3-negative lymphocytes.
- In extreme cases with major histopathological changes, the retinal architecture was widely disintegrated due to an extensive infiltration of inflammatory cells. Remnants of the dead retina are end-stage findings, usually accompanied by minor inflammatory infiltration.
Conclusions
- This research provides evidence of retinal involvement at all stages of ERU, revealing that the disease is driven predominantly by T-cell infiltration. These T-cells were evident in both the mild and severe stages of the disease.
Cite This Article
APA
Deeg CA, Ehrenhofer M, Thurau SR, Reese S, Wildner G, Kaspers B.
(2002).
Immunopathology of recurrent uveitis in spontaneously diseased horses.
Exp Eye Res, 75(2), 127-133.
https://doi.org/10.1006/exer.2002.2011 Publication
Researcher Affiliations
- Institute of Animal Physiology, Ludwig-Maximilians-University, Veterinärstr 13, D-80539, Munich, Germany. deeg@tiph.vetmed.unimuenchen.de
MeSH Terms
- Animals
- Choroid / immunology
- Choroid / pathology
- Ciliary Body / immunology
- Ciliary Body / pathology
- Horse Diseases / immunology
- Horse Diseases / pathology
- Horses
- Iris / immunology
- Iris / pathology
- Optic Disk / immunology
- Optic Disk / pathology
- Photoreceptor Cells, Vertebrate / immunology
- Recurrence
- Retina / immunology
- Retina / pathology
- T-Lymphocytes / immunology
- Uveitis / immunology
- Uveitis / pathology
- Uveitis / veterinary
Citations
This article has been cited 21 times.- Kirmse L, Thieme K, Doherr MG, Eule JC. Evaluation of Laboratory Techniques for the Diagnosis of Leptospira-Associated Equine Recurrent Uveitis (ERU) With Focus on the Goldmann-Witmer Coefficient. Vet Ophthalmol 2026 Jan;29(1):e70132.
- 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).
- Stafford LS, Plummer CE, Smith WC, Gibson DJ, Sharma J, Vicuna V, Diakite S, Larkin J 3rd. A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis. Front Immunol 2024;15:1513157.
- Padjasek M, Qasem B, Cisło-Pakuluk A, Marycz K. Cyclosporine A Delivery Platform for Veterinary Ophthalmology-A New Concept for Advanced Ophthalmology. Biomolecules 2022 Oct 20;12(10).
- 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.
- 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.
- Epps SJ, Coplin N, Luthert PJ, Dick AD, Coupland SE, Nicholson LB. Features of ectopic lymphoid-like structures in human uveitis. Exp Eye Res 2020 Feb;191:107901.
- Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro. Vet Ophthalmol 2020 Jan;23(1):160-170.
- 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.
- Malalana F, Blundell RJ, Pinchbeck GL, Mcgowan CM. The role of Leptospira spp. in horses affected with recurrent uveitis in the UK. Equine Vet J 2017 Nov;49(6):706-709.
- Deeg CA, Amann B, Lutz K, Hirmer S, Lutterberg K, Kremmer E, Hauck SM. Aquaporin 11, a regulator of water efflux at retinal Müller glial cell surface decreases concomitant with immune-mediated gliosis. J Neuroinflammation 2016 Apr 23;13(1):89.
- 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.
- 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.
- Swadzba ME, Hauck SM, Naim HY, Amann B, Deeg CA. Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis. PLoS One 2012;7(12):e50929.
- Szober CM, Hauck SM, Euler KN, Fröhlich KJ, Alge-Priglinger C, Ueffing M, Deeg CA. Profound re-organization of cell surface proteome in equine retinal pigment epithelial cells in response to in vitro culturing. Int J Mol Sci 2012 Oct 31;13(11):14053-72.
- Deeg CA, Eberhardt C, Hofmaier F, Amann B, Hauck SM. Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling. PLoS One 2011;6(12):e27674.
- 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.
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