Matrix metalloproteinase biology applied to vitreoretinal disorders
- Department of Pathology, Institute of Ophthalmology, and Moorfields Eye Hospital, London
- Department of Pathology, Institute of Ophthalmology, London
- Department of Pathology, Institute of Ophthalmology, and Moorfields Eye Hospital, London
- Department of Pathology, Institute of Ophthalmology, and Moorfields Eye Hospital, London
- Department of Pathology, Institute of Ophthalmology, London
- Department of Pathology, Institute of Ophthalmology, and Moorfields Eye Hospital, London
- Department of Pathology, Institute of Ophthalmology, and Moorfields Eye Hospital, London
- Department of Pathology, Institute of Ophthalmology, London
- Department of Pathology, Institute of Ophthalmology, and Moorfields Eye Hospital, London
- Mr C S Sethi, Vitreoretinal Surgery, Moorfields Eye Hospital, City Road, London EC1V 2PD
Matrix metalloproteinases (MMPs) and their inhibitors are believed to have a significant role in a number of vitreoretinal diseases, from proliferative vitreoretinopathy to age related macular degeneration. The aim of this review is to summarise the current knowledge of their involvement in these diseases and to postulate potential therapeutic strategies.
MMPs are a tightly regulated family of zinc dependent endopeptidases that are capable of degrading all components of the extracellular matrix (ECM) and basement membranes.1 The ECM is a complex structure that influences the behaviour of its resident cells, and those in the process of migration, by providing specific contextual information. Enzymes that modify the ECM thus have the potential to affect basic cell biology in many physiological and pathological processes.2 Remodelling of the ECM must occur with spatial and temporal precision for normal development, morphogenesis, homeostasis, and tissue repair.3 As matrix degradation is a prerequisite for malignant invasion and metastasis, it is not surprising that MMP biology has attracted considerable interest, with clinical oncology trials under way in several organ systems.4-7 New proteolytic functions are also being defined for these enzymes. These include the degradation of non-matrix macromolecules such as myelin basic protein, inactivation of α1 antitrypsin, release of sequestered growth factors from ECM, and cleavage of bioactive molecules from the cell surface.8
The tissue inhibitors of metalloproteinases, or TIMPs, are physiological MMP inhibitors that have now been shown to have additional biological activities independent of this primary function.9 The functional proteolytic activity of MMPs in a given biological situation is thus dependent on the relative concentrations of regulatory TIMP molecules andactive MMPs. Excessive MMP activity is associated with matrix degradation and a feature of destructive diseases such as rheumatoid arthritis, osteoarthritis,10 11 dermal photoageing,12periodontitis,13 and chronic …
