Effect of Tear Proteins on Preservative Toxicity to Epithelial Cells

Abstract Eye irritation caused by preservatives in ophthalmic formulations and cosmetics may be affected by the presence of proteins in tears. This hypothesis was investigated by combining preservatives with proteins normally present in tears, that is, albumin, lysozyme, and immunoglobulins, and evaluating them with in vitro models of corneal cytotoxicity. A panel of nine cationic preservatives was tested that included benzalkonium chloride (BAK), a preservative often present in ophthalmic preparations. The studies utilized the vital dyes neutral red and ethidium bromide as indicators of cellular membrane damage. The MDCK epithelial cell line and cultured rabbit corneal epithelial cells were used as ocular models. The results demonstrate that the cytotoxicity of BAK and other preservatives was significantly reduced in the presence of tear proteins. Therefore, the role of tear proteins should be taken into consideration when in vitro tests of eye irritation are conducted.