title: Effects of DA-6034 on aqueous tear fluid secretion and conjunctival goblet cell proliferation.
abstract: OBJECTIVE
  This study was conducted to evaluate the effect of DA-6034, a potent secretagogue, on aqueous tear fluid secretion and its quality in normal rabbit. We also evaluated, in animal models of experimentally induced dry eye disease, its effectiveness over time to stimulate aqueous tear production by ocular ferning test and goblet cell proliferation.
  
  
  METHODS
  Aqueous tear production, total protein levels, and glycoprotein levels in normal rabbits were evaluated after topical application of DA-6034 (0.3, 1, and 3%). Moreover, time course aqueous tear volume measurement and ocular ferning test in tear fluid were performed in dry eyes of rabbits that had been given 1% atropine sulfate, topically. Altogether, tear fluid production and conjunctival goblet cell numbers were measured in dry eyes of mice that had been given topical scopolamine.
  
  
  RESULTS
  Topical application of DA-6034 (0.3, 1, and 3%) significantly increased (P < 0.05) aqueous tear production in a concentration-dependent manner in normal rabbits. There was no change in total protein levels while glycoprotein levels were significantly increased (P < 0.05) at 3% DA-6034. The increase in aqueous tear fluid was significant (P < 0.05) and lasted for 2 h post-instillation in dry eyes of rabbits that had been given 1% atropine sulfate; 10-day repeated instillation of the drug in this model resulted in large and homogeneous fern-like tear patterns. In a mouse model, DA-6034 given as a 3% eyedrop solution significantly increased (P < 0.05) tear fluid production and conjunctival goblet cell number.
  
  
  CONCLUSIONS
  These results suggest that DA-6034 accelerates not only tear secretion but also mucin production and may be a potential therapeutic agent for the treatment of dry eye disease.
authors.affiliation: Research Laboratories, Dong-A Pharmaceutical Company, Kiheung-Gu, Yongin-Shi, Kyunggi-Do, Korea.
authors.forename: Seul Min
authors.initials: SM
authors.lastname: Choi
authors.forename: Yeong Geon
authors.initials: YG
authors.lastname: Lee
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Seo
authors.forename: Kyung Koo
authors.initials: KK
authors.lastname: Kang
authors.forename: Byoung Ok
authors.initials: BO
authors.lastname: Ahn
authors.forename: Moohi
authors.initials: M
authors.lastname: Yoo
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001285:Atropine; D049109:Cell Proliferation / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020397:Goblet Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism; D009883:Ophthalmic Solutions; D011817:Rabbits; D012601:Scopolamine; D013666:Tears / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D005419:Flavonoids; D009077:Mucins; D009883:Ophthalmic Solutions; C042434:tear proteins; D001285:Atropine; D012601:Scopolamine; C121889:recoflavone