Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model.
Abstract: Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloproteinase network in spontaneous uveitis. Methods: Matrix metalloproteinase (MMP) MMP2, MMP9, and MMP14 expression and tissue inhibitor of metalloproteinase (TIMP)-2 and lipocalin 2 (LCN2) expression were analyzed using Western blot quantification. Enzyme activities were examined with zymography. Expression patterns of network candidates were revealed with immunohistochemistry, comparing physiological appearance and changes in a spontaneous recurrent uveitis model. Results: TIMP2 protein expression was found to be decreased in both the vitreous and the retina of a spontaneous model for autoimmune uveitis (equine recurrent uveitis [ERU]), and TIMP2 activity was significantly reduced in ERU vitreous. Functionally associated MMPs such as MMP2, MMP14, and MMP9 were found to show altered or shifted expression and activity. Although MMP2 decreased in ERU vitreous, MMP9 expression and activity were found to be increased. These changes were reflected by profound changes within uveitic target tissue, where TIMP2, MMP9, and MMP14 decreased in expression, whereas MMP2 displayed a shifted expression pattern. LCN2, a potential stabilizer of MMP9, was found prominently expressed in equine healthy retina and displayed notable changes in expression patterns accompanied by significant upregulation in autoimmune conditions. Invading cells expressed MMP9 and LCN2. Conclusions: This study implicates a dysregulation or a change in functional protein-protein interactions in this TIMP2-associated protein network, together with altered expression of functionally related MMPs.
Publication Date: 2011-04-08 PubMed ID: 21228380DOI: 10.1167/iovs.10-6475Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article analyzes the changes in the matrix metalloproteinase network in cases of autoimmune uveitis. It provides an insight, indicating a dysregulation or a shift in protein-protein interactions which could influence the progression of this sight-threatening disease.
Research Methodology
- The researchers in this study employed a range of experimental techniques. They used Western blot quantification to analyze MMP2, MMP9, and MMP14 (matrix metalloproteinases) expressions along with tissue inhibitor of metalloproteinase-2 (TIMP-2) and lipocalin 2 (LCN2) expressions.
- Zymography was used to examine enzyme activities that may have a significant role in the development of the disease.
- Immunohistochemistry was utilized for revealing the expression patterns of network candidates, comparing physiological appearance and changes in a spontaneous recurrent uveitis model.
Experimental Findings
- In the study, the authors observed a decrease in the TIMP2 protein expression in both the vitreous and retina of an autoimmune uveitis model named equine recurrent uveitis (ERU). The activity of TIMP2 was also noticed to have significantly reduced in ERU vitreous.
- MMPs such as MMP2, MMP14, and MMP9 showed altered or shifted expression and activity. Whereas MMP2 decreased in ERU vitreous, MMP9’s expression and activity increased.
- Changes were also noticeable within the uveitic target tissue. TIMP2, MMP9, and MMP14 decreased in expression, while MMP2 experienced a shift in its expression pattern.
- LCN2, a likely stabilizer of MMP9, was found prominently in the healthy equine retina. It showed an upregulation in expression patterns under autoimmune conditions.
- Invading cells were observed to express MMP9 and LCN2, potentially driving the development of uveitis.
Conclusions
- The research implicates a dysregulation or a change in functional protein-protein interactions in this TIMP2-associated protein network. These changes, coupled with altered expression of functionally related MMPs, may significantly contribute to the pathogenesis of autoimmune uveitis.
- The findings provide insights into the molecular mechanisms underlying autoimmune uveitis, which could allow the development of improved therapeutic strategies for this blinding disease.
Cite This Article
APA
Hofmaier F, Hauck SM, Amann B, Degroote RL, Deeg CA.
(2011).
Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model.
Invest Ophthalmol Vis Sci, 52(5), 2314-2320.
https://doi.org/10.1167/iovs.10-6475 Publication
Researcher Affiliations
- Institute of Animal Physiology, Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
MeSH Terms
- Animals
- Autoimmune Diseases / enzymology
- Autoimmune Diseases / veterinary
- Blotting, Western
- Disease Models, Animal
- Fluorescent Antibody Technique, Indirect
- Horse Diseases / enzymology
- Horses
- Lipocalins / metabolism
- Matrix Metalloproteinases / metabolism
- Recurrence
- Retina / enzymology
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Uveitis / enzymology
- Uveitis / veterinary
- Vitreous Body / enzymology
Citations
This article has been cited 17 times.- Rakib-Uz-Zaman SM, Werner L, Duncan MK. Unanswered questions regarding the pathogenesis of late onset posterior capsular opacification. Front Ophthalmol (Lausanne) 2025;5:1680042.
- Xu R, Zheng J, Liu L, Zhang W. Effects of inflammation on myopia: evidence and potential mechanisms. Front Immunol 2023;14:1260592.
- Batsos G, Christodoulou E, Christou EE, Galanis P, Katsanos A, Limberis L, Stefaniotou M. Vitreous inflammatory and angiogenic factors on patients with proliferative diabetic retinopathy or diabetic macular edema: the role of Lipocalin2. BMC Ophthalmol 2022 Dec 19;22(1):496.
- Kim MH, Lim SH. Matrix Metalloproteinases and Glaucoma. Biomolecules 2022 Sep 25;12(10).
- 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).
- Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
- Weinreb RN, Robinson MR, Dibas M, Stamer WD. Matrix Metalloproteinases and Glaucoma Treatment. J Ocul Pharmacol Ther 2020 May;36(4):208-228.
- Lipski DA, Foucart V, Dewispelaere R, Caspers LE, Defrance M, Bruyns C, Willermain F. Retinal endothelial cell phenotypic modifications during experimental autoimmune uveitis: a transcriptomic approach. BMC Ophthalmol 2020 Mar 17;20(1):106.
- Ghosh S, Stepicheva N, Yazdankhah M, Shang P, Watson AM, Hose S, Liu H, Weiss J, Zigler JS Jr, Valapala M, Watkins SC, Sinha D. The role of lipocalin-2 in age-related macular degeneration (AMD). Cell Mol Life Sci 2020 Mar;77(5):835-851.
- Batsos G, Christodoulou E, Vartholomatos G, Galanis P, Stefaniotou M. Vitreous levels of Lipocalin-2 on patients with primary rhegmatogenous retinal detachment. PLoS One 2019;14(12):e0227266.
- Haneda S, Nagaoka K, Nambo Y, Kikuchi M, Nakano Y, Li J, Matsui M, Miyake YI, Imakawa K. Expression of uterine lipocalin 2 and its receptor during early- to mid-pregnancy period in mares. J Reprod Dev 2017 Apr 21;63(2):127-133.
- Zhou YS, Xu J, Peng J, Li P, Wen XJ, Liu Y, Chen KZ, Liu JQ, Wang Y, Peng QH. Research progress of stem cells on glaucomatous optic nerve injury. Int J Ophthalmol 2016;9(8):1226-9.
- Velez G, Roybal CN, Colgan D, Tsang SH, Bassuk AG, Mahajan VB. Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease. JAMA Ophthalmol 2016 Apr;134(4):444-8.
- De Groef L, Andries L, Lemmens K, Van Hove I, Moons L. Matrix metalloproteinases in the mouse retina: a comparative study of expression patterns and MMP antibodies. BMC Ophthalmol 2015 Dec 29;15:187.
- 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.
- Jiang Y, Zhang Y, Zhang L, Wang M, Zhang X, Li X. Therapeutic effect of bone marrow mesenchymal stem cells on laser-induced retinal injury in mice. Int J Mol Sci 2014 May 27;15(6):9372-85.
- 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.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists