Francesca Liva, Doretta Cuffaro, Elisa Nuti, Susanna Nencetti, Elisabetta Orlandini, Giovanni Vozzi and Armando Rossello* Pages 903 - 918 ( 16 )
Background: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced Retinal Pigment Epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular matrix (ECM) turnover and, in turn, in ECM pathologies, such as AMD. A balance between the activities of MMPs and Tissue Inhibitors of Metalloproteinase (TIMPs) is crucial for the integrity of the ECM components; indeed, a dysregulation in the ratio of these factors produces profound changes in the ECM, including thickening and deposit formation, which eventually might lead to AMD development.
Objective: This article reviews the relevance and impact of zinc metalloproteinases on the development of AMD and their roles as biomarkers and/or therapeutic targets. We illustrate some studies on several inhibitors of MMPs currently used to dissect physiological properties of MMPs. Moreover, all molecules or technologies used to control MMP and ADAM activity in AMD are analyzed.
Conclusion: This study underlines the changes in the activity of MMPs expressed by RPE cells, highlights the functions of already used MMP inhibitors and consequently suggests their application as therapeutic agents for the treatment of AMD.
AMD, RPE, MMPs, ADAMs, ADAMTSs, MMP inhibitors.
Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Research Center , Research Center , Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa