Influence of Matrix Metalloproteinases MMP-2, -3 and on Age- Related Macular Degeneration Development

Abstract

Age-related macular degeneration (AMD) is the leading cause of significant and irreversible central visual loss as it affects a small area of the retina, called the macula. However, the pathogenesis of still fairly understood. AMD has a multifactorial etiology, and its development might be influenced by body peculiarities, environmental and genetic factors. Risk factors such as age, gender, cigarette smoking, color of iris, nutrition, body mass index, oxidative stress, and genetic factors (complement factor H gene, Apo E gene, matrix metalloproteinases (MMPs) genes and others) increase probability to develop AMD. Here, we discuss about choroidal neovascularization process, where hypoxia, inflammatory process, and proteolytic enzymes play a main role, but mainly we focus on the family of matrix metalloproteinases (MMPs), especially on MMP-2,-3 and-9, and their impact on AMD development. MMPs belong to a family of proteolytic zinccontaining enzymes, and their mechanism under normal physiological conditions is precisely regulated, but when is dysregulated, MMPs become a cause of various diseases, including and AMD. MMPs are capable of degrading most of the extracellular matrix components, which are important in the remodeling during angiogenesis. Angiogenesis is the main pathological process associated with age-related macular degeneration development. Activated endothelial cells release MMPs which by degrading the basilar membrane allows capillaries to grow beneath the retina and retinal layers. Such capillaries often bleed, more liquids are filtered through the walls, and fibrous tissue grows within. Furthermore, swelling of the retina and impaired vision occur. In this book chapter, we focus on AMD prevalence, risk factors, clinics, diagnostics and influence of MMP-2,-3 and-9 on AMD development.

Saffron: A Multitask Neuroprotective Agent for Retinal Degenerative Diseases

“…Activation of the matrix metalloproteinases is pivotal in the remodeling of the extracellular matrix and MMP-3 is usually involved in such activation mechanisms. The presence of other MMPs, namely MMP-2 and -9, in their inactive forms has been reported in the human Bruch’s membrane [35]. It can be speculated that MMP-3 released from the vesicle-like structure in the Muller glia, after light induction, could induce extra-direct proteolytic activity and/or a specific activation of other proteases such MMP-2 and -9.…”

Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD)

“…Secondly, it is important to note that AMD has different stages, in which MMPs could play different roles; not all the studies have taken into account this tenet. Generally, decreased levels of MMP-2 and MMP-9 have been related with the thickening of the BM as well as early stages of AMD, while the overexpression of MMP-2 has been associated with the development of CNV [185].…”