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Salman Porbandarwalla, Kelly Green, Randolph Glickman, William Sponsel, John Denny, Neeru Kumar; Phthalates Released From IOLs Affect Protein Expression In Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):281.
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© ARVO (1962-2015); The Authors (2016-present)
On rare instances foldable acrylic intraocular lenses (IOLs) may require removal due to breaks in the haptics, lens surface cracks or manufacturing defects. In our previous study, these IOLs were shown to release bis-2-ethylhexyl phthalate (DEHP) after careful lens bisection in situ. The purpose of this study is to determine if DHEP affects cellular signaling that may underlie the inflammatory response seen in some patients following bisection and removal of their IOL.
Chemical analysis of acrylate-methacrylate lenses was performed by gas chromatography electron impact ionization mass spectrometry. The structures of liberated chemical compounds were confirmed with NMR spectroscopy. In vitro cultures of lens epithelial cells (ATCC CRL-11421) were exposed to DHEP in cell culture medium to determine effects on viability, assayed by the MTT test. To determine effects on protein expression, the cells were exposed to DHEP at a dose of 50 µg/ml for 48 hours. The cells were lysed and the solubilized proteins were analyzed by 2-D gel electrophoresis.
Cultured human lens epithelial cells exposed to increasing levels of the identified phthalate exhibited a dose-dependent loss of viability, at a phthalate concentration as low as 20 µg/ml. In protein extracts from human lens cells exposed for 48 hours of 50 µg/ml phthalate, 7 proteins with ≥2-fold difference in expression level from control were identified, indicating that DHEP may affect cell function through interaction with one or more signaling pathways.
The presence of unique proteins in the phthalate-exposed human lens epithelial cells shows that exposure to a low concentration of DHEP modulates the cellular response to these agents, raising the possibility of a toxic response in other ocular tissues. The goal of current work is to sequence and identify these unique proteins in order to characterize the affected cellular signaling pathways. DHEP is closely related to Bisphenol A that has been associated with adverse effects, including but not limited to tumorigenesis, DNA methylation, diabetes, heart disease and growth retardation.
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