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Christian Wertheimer, Stefan Kassumeh, Nick P. Piravej, Olga Nilmayer, Christian Braun, Claudia Priglinger, Nikolaus Luft, Armin Wolf, Wolfgang J. Mayer, Siegfried G. Priglinger, Kirsten H. Eibl-Lindner; The Intraocular Lens as a Drug Delivery Device: In Vitro Screening of Pharmacologic Substances for the Prophylaxis of Posterior Capsule Opacification. Invest. Ophthalmol. Vis. Sci. 2017;58(14):6408-6418. doi: 10.1167/iovs.17-22555.
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Numerous pharmacologic substances have been proposed for preventing posterior capsule opacification (PCO). The following trial was to compare those drugs to find more suitable options. IOL should then be modified by the pharmaceuticals as a drug-delivery device.
A systematic literature search was performed to identify published substances. FHL-124 was used to determine cell proliferation and toxicity using a dye reduction test (XTT). Prescreened substances showing a reduction on cell growth without being toxic were soaked into an IOL. Those IOL were tested for their effect on PCO in an anterior-segment model and the human ex vivo capsular bag model. Toxicity on a corneal endothelial cell line (CEC-SV40) was determined. Release kinetics of methotrexate from the IOL was measured. Toxicity testing in both cell lines was done in serum-free conditions. All growth assays were exposed to 10% fetal calf serum (FCS)-supplemented medium.
The substances inhibited cell growth at the following EC50: caffeic acid phenethyl ester 1.6 ± 0.9 nM, disulfiram 359 ± 33 nM, methotrexate 98.0 ± 29.7 nM, rapamycin 70.2 ± 14.0 pM, and retinoic acid 1.1 ± 0.12 nM. All but disulfiram showed an effect in the anterior segment model when soaked into an IOL. Long-term inhibitory effects in the human capsular bag model were observed for caffeic acid phenethyl ester and methotrexate IOLs. Only methotrexate and disulfiram did not show any toxicity on endothelial cells. Methotrexate was released constantly from the hydrophilic IOL for 2 weeks.
We could identify caffeic acid phenethyl ester and methotrexate in vitro as potential candidates for IOL modification for PCO prophylaxis.
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