Kojima Takashi, Dogru Murat, Ibrahim Osama M, Nagata Taeko, Higa Kazunari, Shimizu Takahiko, Shirasawa Takuji, Satake Yoshiyuki, Shimazaki Seika, Shimazaki Jun, Tsubota Kazuo
Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan ; Department of Ophthalmology, Tokyo Dental College, Ichikawa, Chiba, Japan.
Mol Vis. 2014 Jun 28;20:929-38. eCollection 2014.
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.
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.
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.
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.
研究一种水和粘蛋白促分泌剂(3% 地夸磷索钠滴眼液)与野生型(WT)小鼠相比,对Sod1基因敲除(Sod1(-/-))小鼠泪液功能和结膜眼表变化的作用。
本研究中,在40周龄时检查了7只C57BL背景的Sod1(-/-)雄性小鼠的14只眼睛和7只C57BL6品系野生型雄性小鼠的14只眼睛。所有小鼠每天应用3%地夸磷索眼药水6次,持续2周。通过荧光素和孟加拉玫瑰红染色评估泪膜稳定性和角膜上皮损伤。在滴眼药水前后进行眼前节照相。用酚红浸渍棉线在未麻醉状态下测量水样泪液量。在接受地夸磷索治疗42周后处死动物,将整个眼球标本进行过碘酸希夫染色。用J Image软件对杯状细胞密度进行定量分析。还进行了结膜粘蛋白5AC信使核糖核酸表达的定量实时聚合酶链反应。
在滴眼药水前,Sod1(-/-)小鼠的荧光素染色评分显著高于WT小鼠。WT小鼠和基因敲除小鼠经地夸磷索治疗后,平均泪膜破裂时间、孟加拉玫瑰红染色评分和粘蛋白5信使核糖核酸表达均显著改善。治疗后,Sod1(-/-)小鼠的平均荧光素染色评分和水样泪液量显著改善。应用地夸磷索眼药水2周后,在所有标本中均可确认杯状细胞显著且持续增加,炎症细胞浸润减少。
在这个与年龄相关的干眼病小鼠模型中,3%地夸磷索眼药水似乎对眼表疾病的治疗有效。