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18 June 2014 : Review article  

Age-related macular degeneration and changes in the extracellular matrix

Małgorzata NitaABCDEFG, Barbara Strzałka-MrozikABCDEF, Andrzej GrzybowskiABCDEF, Urszula MazurekABCDEF, Wanda RomaniukABCDEF

DOI: 10.12659/MSM.889887

Med Sci Monit 2014; 20:1003-1016

Abstract

Age-related macular degeneration (AMD) is the leading cause of permanent, irreversible, central blindness (scotoma in the central visual field that makes reading and writing impossible, stereoscopic vision, recognition of colors and details) in patients over the age of 50 years in European and North America countries, and an important role is attributed to disorders in the regulation of the extracellular matrix (ECM). The main aim of this article is to present the crucial processes that occur on the level of Bruch’s membrane, with special consideration of the metalloproteinase substrates, metalloproteinase, and tissue inhibitor of metalloproteinase (TIMP). A comprehensive review of the literature was performed through MEDLINE and PubMed searches, covering the years 2005–2012, using the following keywords: AMD, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases, Bruch’s membrane, collagen, elastin. In the pathogenesis of AMD, a significant role is played by collagen type I and type IV; elastin; fibulin-3, -5, and -6; matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, and MMP-1; and TIMP-3. Other important mechanisms include: ARMS2 and HTR1 proteins, the complement system, the urokinase plasminogen activator system, and pro-renin receptor activation. Continuous rebuilding of the extracellular matrix occurs in both early and advanced AMD, simultaneously with the dysfunction of retinal pigment epithelium (RPE) cells and endothelial cells. The pathological degradation or accumulation of ECM structural components are caused by impairment or hyperactivity of specific MMPs/TIMPs complexes, and is also endangered by the influence of other mechanisms connected with both genetic and environmental factors.

Keywords: Matrix Metalloproteinases - metabolism, Macular Degeneration - pathology, Extracellular Matrix - pathology, Tissue Inhibitor of Metalloproteinases - metabolism, Wet Macular Degeneration - pathology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750