title: The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice.
abstract: OBJECTIVE
  To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1(-/-) in comparison to the wild-type (WT) mice.
  
  
  METHODS
  Fourteen eyes of 7 Sod1(-/-) male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed.
  
  
  RESULTS
  Sod1(-/-) mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1(-/-) mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application.
  
  
  CONCLUSIONS
  Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan ; Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan.
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Osama M
authors.initials: OM
authors.lastname: Ibrahim
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Higa
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Aging Control Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.affiliation: Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Satake
authors.affiliation: Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan.
authors.forename: Seika
authors.initials: S
authors.lastname: Shimazaki
authors.affiliation: Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000473:pathology; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000187:drug effects / Q000473:pathology; D005123:Eye / Q000187:drug effects*; D019793:Fluorescein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D011122:Polyphosphates / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012395:Rose Bengal / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013666:Tears / Q000187:drug effects*; D013997:Time Factors; D014500:Uracil Nucleotides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D055271:Mucin 5AC; D011122:Polyphosphates; D012333:RNA, Messenger; D014500:Uracil Nucleotides; D012395:Rose Bengal; C403315:diquafosol; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019793:Fluorescein