Effects of DA-6034, a Flavonoid Derivative, on Mucin-like Glycoprotein and Ocular Surface Integrity in a Rabbit Model

Abstract

This study was designed to assess whether DA-6034 (7-carboxymethyloxy-3′,4′,5-trimethoxy flavone monohydrate), a new synthetic derivative of eupatilin, increases secretion of mucin-like glycoprotein and some mucins species in conjunctiva and cornea, and contributes to the preservation of ocular surface integrity. Human conjunctival and corneal epithelial cells were incubated with DA-6034 (1–250 µM). To investigate mucin secreting activity more directly, isolated rat conjunctival goblet cells were also used. Corneal protection was investigated using a desiccation-induced rabbit model of dry eye syndrome. It was found that DA-6034 increased mucin-like glycoprotein levels of both conjunctival and corneal epithelial cells at concentrations above 100 µM. Using human conjunctival epithelial cells, it was demonstrated that treatment with DA-6034 (200 µM) significantly increased production of some mucins species including MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC16. DA-6034 also significantly increased MUC5AC production from conjunctival goblet cells isolated from rats. In the rabbit desiccation model, an ophthalmic suspension containing 3% DA-6034 significantly reduced corneal damage induced by desiccation. These results suggest that DA-6034 is a good candidate for treatment of dry eye through maintaining ocular surface integrity, which might be related to mucin secretion.

Key words

DA-6034 - Dry eye - Flavonoid derivative - Mucin-like glycoprotein - Ocular surface integrity - Ophthalmic drugs

• Literature

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