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Abstract #21131 Published in IGR 10-2
In vitro cytotoxicity of eight β-blockers in human corneal epithelial and retinal pigment epithelial cell lines: Comparison with epidermal keratinocytes and dermal fibroblasts
Cheong HI; Johnson J; Cormier M; Hosseini KToxicology in Vitro 2008; 22: 1070-1076
β-Blockers are a class of agents that have been used extensively in topical preparations for the treatment of glaucoma. Recent evidence indicates that they may also be useful in a number of retinal diseases. Because biocompatibility is of utmost importance in the treatment of ocular-related diseases, we compared the in vitro cytotoxicity, using the MTT assay, of eight clinically available β-blockers (propranolol, alprenolol, atenolol, labetalol, metoprolol, pindolol, timolol, and bisoprolol) on human corneal epithelial and retinal pigment epithelial cell lines. Primary and immortalized corneal and retinal cell lines were compared for their susceptibility to the cytotoxic effect of the drugs. The cytotoxicity of β-blockers was also evaluated on human skin keratinocytes and fibroblasts in order to investigate susceptibility differences as a function of the tissue of origin. Results demonstrated large differences in cytotoxicity (about 60-fold) for these closely related drugs on the same cell line. Conversely, only relatively small differences in cytotoxicity were observed between the different cell lines for the same drug, indicating that the mechanism of cytotoxicity is not cell-specific. Calculation of the ratio between the cytotoxicity of β-blockers and their β-blocking constant is presented as a potential tool to help identify the least irritating, most potent drug.
Dr. M. Cormier, ALZA Corporation, Drug Device R and D, 1900 Charleston Rd., Mountain View, CA 94043, USA. Michel.cormier@sbcglobal.net
Classification:
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
2.2 Cornea (Part of: 2 Anatomical structures in glaucoma)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
