ABSTRACT
Cataract surgery, while the most common surgical procedure performed, leads to posterior capsule opacification in approximately 30% of cases. Transforming growth factor beta 2 (TGF-ß2) and matrix metalloproteinases (MMPs) have been shown to play important roles in the cellular processes leading to posterior capsule opacification. Delivery of inhibitors to MMPs may have the potential to inhibit the initial cascade of events that lead to PCO. However, delivery of these molecules via tethering has proven difficult. In this work, sulfadiazine was tethered to polydimethylsiloxane (PDMS) via a polyethylene glycol (PEG) spacer as a potential MMPI mimic. Surface characterization using a variety of methods demonstrated successful modification with the antibiotic. The surfaces were examined with lens epithelial cells to determine their effect on these cellular processes, including cell transdifferentiation and production of extracellular matrix components. The presence of TGF-ß2 in the cell culture media was found to stimulate the production of ECM components such as collagen, fibronectin, and laminin, as well as alpha smooth muscle actin (α-SMA), and the migration marker Rho by HLE-B3 and FHL124 cells. In all cases, these effects were decreased but not completely eradicated by the presence of sulfadiazine on the PDMS surfaces. While the level of inhibition necessary for inhibition of PCO in vivo is unknown, these results suggest that IOL surface modification with sulfadiazine has the potential to reduce cellular changes associated with PCO. Furthermore, the results demonstrate for the first time that changes consistent with inhibition of fibrosis may be elicited by surfaces modified with sulfadiazine.
Subject(s)
Capsule Opacification/drug therapy , Dimethylpolysiloxanes/chemistry , Sulfadiazine/therapeutic use , Actins/metabolism , Cell Communication/drug effects , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Collagen/metabolism , Fibronectins/metabolism , Humans , Infant , Laminin/metabolism , Lens, Crystalline/drug effects , Lens, Crystalline/pathology , Mass Spectrometry , Photoelectron Spectroscopy , Polyethylene Glycols/chemistry , Spectroscopy, Fourier Transform Infrared , Sulfadiazine/pharmacology , Surface Properties , Water/chemistry , rho GTP-Binding Proteins/metabolismABSTRACT
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.