Effects of DA-6034, a flavonoid derivative, on mucin-like glycoprotein and ocular surface integrity in a rabbit model.
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 microM). 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 microM. Using human conjunctival epithelial cells, it was demonstrated that treatment with DA-6034 (200 microM) 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.
Choi
Seul Min
SM
Research Laboratories, Dong-A Pharmaceutical Company, Kyunggi-do, Korea.
Seo
Mi Jeong
MJ
Lee
Yeong Geon
YG
Lee
Min Jung
MJ
Jeon
Hyung Jun
HJ
Kang
Kyung Koo
KK
Ahn
Byoung Ok
BO
Yoo
Moohi
M
D000818:Animals; D002460:Cell Line; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003681:Dehydration / Q000473:pathology; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009077:Mucins / Q000378:metabolism*; D011817:Rabbits; D051381:Rats
D005419:Flavonoids; D006023:Glycoproteins; D009077:Mucins; C121889:recoflavone