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.