Modification of PDMS as a Model IOL With Sulfadiazine Decrease TGF-β2-Stimulated Production of ECM Components and Cell Adhesion

Abstract

Purpose: : Wound healing following cataract surgery results in epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs). This leads to the generation of fibroblastic cells, accumulation of extra cellular matrix (ECM) components such as fibronectin, laminin, and collagen and posterior capsule opacification (PCO). Transforming growth factor beta 2 (TGF-β₂), a cytokine and modulator of cell proliferation, migration, and ECM synthesis, is known to play a key role in PCO. It stimulates secretion of matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 which play an important role in cell migration by degradation of ECM components. It was hypothesized that delivery of sulfadiazine as an MMP inhibitor via the intraocular lens (IOL) may lead to a decrease in the adhesion, and transformation of LECs in vitro and ultimately will impact the formation of PCO in vivo.

Methods: : Sulfadiazine was loaded into PDMS or tethered to the surface of PDMS using a previously established method. The surface was characterized using ATR-FTIR, contact angle, XPS, and TOF-SIMS. Surface morphological properties were measured by profilometry and SEM. Interactions of the modified and unmodified PDMS with human lens epithelial cell lines HLE-B3 and FHL124 were examined. Specifically, the production of the fibroblast marker -SMA and ECM components such as fibronectin, laminin, and collagen were measured with and without TGF-β₂ stimulation. Results were compared to determine efficacy and the most appropriate delivery method for the drug.

Results: : Sulfadiazine release was measured under simulated in vitro conditions. Release occurred over a period of 4 months with an initial burst of 3-30% in the first 2 hours. Surface modification was confirmed by water contact angles and the presence of representative peaks in the XPS and ATR-FTIR. Viability of lens epithelial cells, measured by MTT assay, demonstrated that modification with sulfadiazine alters cellular proliferation. However, treatment with TGF-β₂ increased cell adhesion and ECM production while presence of the drug was found to decrease production of -SMA, and ECM components including collagen, fibronectin, and laminin leading to lower HLE-B3 and FHL124 cells adhesion.

Conclusions: : TGF-β₂ promoted HLE-B3 and FHL124 cells adhesion by inducing the production of ECM components including collagen, fibronectin, and laminin. Introduction of sulfadiazine to PDMS as a model IOL inhibits the production of these TGF-β₂ induced ECM components leading to decreased cell adhesion. This method of surface modification could therefore be a potential indication for the prevention of PCO.

Keywords: posterior capsular opacification (PCO) • intraocular lens • extracellular matrix