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F. Brignole-Baudouin, H. Liang, A. Pauly, L. Riancho, C. Baudouin; Toxicological Evaluation of Preservative-Containing and Preservative-Free Prostaglandin Analogs on the 3d-Reconstituted Corneal Epithelium (SkinethicTM) System. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2371.
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Using an established three-dimensional (3D) toxicological model based on reconstituted human corneal epithelium (HCE), this study investigated the tolerability of four topical intraocular pressure (IOP)-lowering agents: the commercial solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost containing 0.02%, 0.015%, and 0.005% benzalkonium chloride (BAC), respectively and the preservative-free (PF) tafluprost. Solutions of 0.01% and 0.02%BAC alone were also evaluated for comparison.
The 3D-HCEs were treated with the test solutions for 24 hours followed or not by a 24-hour recovery period. We used a modified MTT procedure to assess cell viability in the HCEs. Frozen sections were analyzed using fluorescence microscopy for the evaluation of apoptosis (TUNEL), inflammation (ICAM-1), and proliferation (Ki67). Corneal epithelial tight junctions (occludin and ZO-1) were also assessed by en-face confocal microscopy in response to the different eye drops.
The MTT test revealed the cytotoxicity of these antiglaucoma eye drops that was primarily related to the concentration of their common BAC preservative (0.02%BAC-latanoprost > 0.015%BAC-travoprost > 0.005%BAC-bimatoprost). PF-tafluprost did not induce obvious cytotoxicity and showed the least expression of inflammatory or apoptotic markers and revealed preservation of membrane immunostaining of tight junction proteins in comparison with BAC-containing solutions.
The toxicological model of 3D reconstructed corneal epithelium model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous solutions. Compared to the formulations containing the BAC, in this 3D model, PF-tafluprost was well tolerated without inducing significant corneal epithelium deterioration.
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