title: Sulfadiazine modified PDMS as a model material with the potential for the mitigation of posterior capsule opacification (PCO).
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-β2) 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-β2 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.
authors.affiliation: School of Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON L8S 4L7, Canada.
authors.forename: Bahram
authors.initials: B
authors.lastname: Amoozgar
authors.affiliation: School of Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON L8S 4L7, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Morarescu
authors.affiliation: School of Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON L8S 4L7, Canada; Department of Chemical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON L8S 4L7, Canada. Electronic address: sheardow@mcmaster.ca.
authors.forename: Heather
authors.initials: H
authors.lastname: Sheardown
mesh_terms: D000199:Actins / Q000378:metabolism; D058442:Capsule Opacification / Q000188:drug therapy*; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007797:Laminin / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000473:pathology; D013058:Mass Spectrometry; D056951:Photoelectron Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013411:Sulfadiazine / Q000494:pharmacology / Q000627:therapeutic use*; D013499:Surface Properties; D014867:Water / Q000737:chemistry; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D004129:Dimethylpolysiloxanes; D005353:Fibronectins; D007797:Laminin; D014867:Water; D013411:Sulfadiazine; D011092:Polyethylene Glycols; D003094:Collagen; D020741:rho GTP-Binding Proteins
keywords: Epithelial to mesenchymal transition (EMT); Intraocular lens (IOL); Matrix metalloproteinase (MMP); Posterior capsule opacification (PCO); Transforming growth factor beta 2 (TGF-β(2))