title: Effect of delivery of MMP inhibitors from PDMS as a model IOL material on PCO markers.
abstract: Posterior capsule opacification (PCO) or secondary cataract formation, following intraocular lens implantation, is a significant complication affecting an estimated 28% of cataract patients. Matrix metalloproteinases (MMPs) have been demonstrated to play a role in the formation of anterior subcapsular cataracts and it has been shown that the presence of MMP inhibitors (MMPI) decreases subcapsular cataract formation ex vivo. Since the mechanisms responsible for anterior subcapsular cataract formation and posterior capsule opacification are similar, it is reasonable to suggest that MMP inhibitors may also mitigate PCO. One of the most effective ways of delivering the inhibitors may be from the implanted intraocular lens (IOL) material itself. In the current work, delivery of three different MMP inhibitors from silicone rubber as a model IOL material was examined. Loading methods were developed which allowed continuous release of active MMPI for periods of over 5 months in some cases. Reduced migration rates were observed in human lens epithelial cells in vitro, suggesting that an effect on PCO may be possible. While further studies are necessary to tune the systems to achieve the desired rates of release, this work demonstrates that delivery of MMPI from silicone IOL materials has the potential to decrease the incidence of PCO.
authors.affiliation: School of Biomedical Engineering, Department of Chemical Engineering, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Morarescu
authors.forename: Judy A
authors.initials: JA
authors.lastname: West-Mays
authors.forename: Heather D
authors.initials: HD
authors.lastname: Sheardown
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002386:Cataract / Q000473:pathology; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007903:Lens Capsule, Crystalline / Q000473:pathology; D007910:Lenses, Intraocular; D008422:Materials Testing; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D055213:Retinal Pigment Epithelium / Q000166:cytology; D012826:Silicone Elastomers / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D012826:Silicone Elastomers