Marie Krogh Nielsen1,2, Yousif Subhi1,2, Christopher Rue Molbech1,2, Line Lynge Nilsson2,3, Mogens Holst Nissen4, Torben Lykke Sørensen1,2. 1. Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark. 2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 3. Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital, Roskilde, Denmark. 4. Eye Research Unit, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Abstract
PURPOSE: Tissue inhibitor of metalloproteinase (TIMP) is known to play a role in age-related macular degeneration (AMD). We wished to investigate alterations in different late stages of AMD: neovascular AMD and geographic atrophy (GA). METHODS: This was a prospective case-control study. A total of 125 participants were included consecutively during a period of 18 months. We included 46 patients with neovascular AMD, 46 patients with GA without any sign of choroidal neovascularization in either eye, and 33 healthy aged controls. Patients with immune-affecting disorders were not included. Commercial immunoassay kits were used to quantify levels of TIMP-1, TIMP-3, MMP-2 and MMP-9 in blood plasma. RESULTS: We found that patients with neovascular AMD had lower plasma concentration of TIMP-3 (p = 0.028) than healthy controls. Patients with GA had higher plasma levels of TIMP-1 (p < 0.001) and MMP-9 (p = 0.022) compared to healthy controls. Also, we found that TIMP-1 levels in patients with GA increased with age (Spearman's rho = 0.04, p = 0.006). CONCLUSION: Matrix metalloproteinases (MMPs) and TIMPs, which are known to be involved in age-related changes in Bruch's membrane, are significantly altered systemically, suggesting the presence of an imbalance in the homeostasis of the extracellular matrix. These imbalances may explain differences in the clinical manifestation of late AMD.
PURPOSE:Tissue inhibitor of metalloproteinase (TIMP) is known to play a role in age-related macular degeneration (AMD). We wished to investigate alterations in different late stages of AMD: neovascular AMD and geographic atrophy (GA). METHODS: This was a prospective case-control study. A total of 125 participants were included consecutively during a period of 18 months. We included 46 patients with neovascular AMD, 46 patients with GA without any sign of choroidal neovascularization in either eye, and 33 healthy aged controls. Patients with immune-affecting disorders were not included. Commercial immunoassay kits were used to quantify levels of TIMP-1, TIMP-3, MMP-2 and MMP-9 in blood plasma. RESULTS: We found that patients with neovascular AMD had lower plasma concentration of TIMP-3 (p = 0.028) than healthy controls. Patients with GA had higher plasma levels of TIMP-1 (p < 0.001) and MMP-9 (p = 0.022) compared to healthy controls. Also, we found that TIMP-1 levels in patients with GA increased with age (Spearman's rho = 0.04, p = 0.006). CONCLUSION: Matrix metalloproteinases (MMPs) and TIMPs, which are known to be involved in age-related changes in Bruch's membrane, are significantly altered systemically, suggesting the presence of an imbalance in the homeostasis of the extracellular matrix. These imbalances may explain differences in the clinical manifestation of late AMD.
Authors: Luis García-Onrubia; Fco Javier Valentín-Bravo; Rosa M Coco-Martin; Rogelio González-Sarmiento; J Carlos Pastor; Ricardo Usategui-Martín; Salvador Pastor-Idoate Journal: Int J Mol Sci Date: 2020-08-18 Impact factor: 5.923
Authors: Emine Cinici; Ozge Caglar; Mehmet Enes Arslan; Nilay Dilekmen; Bahadır Utlu; Adil Mardinoglu; Hasan Turkez Journal: Biomed Res Int Date: 2021-02-02 Impact factor: 3.411
Authors: Bruno Nobre Lins Coronado; Felipe Bruno Santos da Cunha; Raphaela Menezes de Oliveira; Otávio de Toledo Nóbrega; Carlos André Ornelas Ricart; Wagner Fontes; Marcelo Valle de Sousa; Marcos Pereira de Ávila; Aline Maria Araújo Martins Journal: Front Med (Lausanne) Date: 2022-01-27