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
