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H. Liang, C. Baudouin, P. Daull, J.-S. Garrigue, F. Baudouin; In vitro and in vivo Evaluation of Newly Developed Cationic Emulsion Formulations in Corneal Wound Healing Models. Invest. Ophthalmol. Vis. Sci. 2010;51(13):378.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have demonstrated that benzalkonium chloride (BAC) altered the ocular surface while new cationic emulsion (CE) formulations were well tolerated without inducing ocular surface damages. The aim of this study was to investigate the effects of eye drops on wound healing in both in vitro (1) and in vivo (2) models.
(1) A wound was made by scratching through a confluent cell layer of immortalized human corneal epithelial cells. Cytotoxicity, cell migration and proliferation were analyzed 2 and 24 h after a 30 min exposure of the different eye drops. Immunostainings were performed for actin, occludin, TUNEL and Ki67. (2) A size-standardized half superior part of corneal epithelium was removed in twenty rats. Rats (4 per group) were instilled bid for 5 days (D): sterile PBS, 0.02%BAC, 0.02%BAC-latanoprost, CE, and latanoprost-CE. At D5, the recovery and integrity of the corneal epithelium was assessed.
Exposure of ocular surface to 0.02%BAC or 0.02%BAC-latanoprost delayed corneal healing by inducing an important inflammatory response. In the same time MUC5AC expression was markedly decreased. CE- and latanoprost-CE-treated rats showed almost normal corneal surface, with very little scar tissue. In vitro data confirmed that there was no difference between CE formulations and PBS.
These models both evaluated the cytotoxicity and dynamic wound healing capabilities of ophthalmic solutions. BAC-containing solutions delayed the wound healing processes, while cationic emulsions favoured healing. The latanoprost-cationic emulsion may protect the ocular surface and improve long-term tolerance over BAC-containing glaucoma treatments. Moreover, the correlation of in vivo and in vitro data confirmed the potential of the latter model as a reliable alternative to in vivo ocular toxicity tests.
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