1 Pharmaceutical Research Laboratories No.1, Research and Development Headquarters , Lion Corporation, Kanagawa, Japan .
2 Department of Ophthalmology, Juntendo University Shizuoka Hospital , Shizuoka, Japan .
J Ocul Pharmacol Ther. 2017 Jan/Feb;33(1):24-33. doi: 10.1089/jop.2015.0161. Epub 2016 Dec 23.
We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury.
The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal.
Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P < 0.05) and 7 days (P < 0.01). Significant increases in corneal rMuc4 and conjunctival rMuc5AC after 1 day (P < 0.01) and conjunctival rMuc16 gene expression after 3 days were observed with VApal treatment (P < 0.05). Furthermore, conjunctival MUC16 expression significantly increased after 3 days of VApal treatment (P < 0.05).
VApal promoted corneal rMuc4, conjunctival rMuc5AC, and conjunctival rMuc16 gene expression in a rat dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.
我们研究了视黄醇棕榈酸酯(VApal)对泪腺(LG)切除后大鼠干眼病模型中粘蛋白基因和蛋白表达的伤口愈合作用。
通过手术切除雄性 Long-Evans 大鼠的主要 LG 制备大鼠干眼病模型。在双侧下睑结膜中央碱性损伤后,一只眼滴用 1500IU/ml 的 VApal 滴眼液,另一只眼滴用对照剂,每天 6 次,共 7 天。用 VApal 治疗 1、3、(5)和 7 天后,通过实时聚合酶链反应或酶联免疫吸附试验分析角膜和结膜中 MUC1、MUC4、MUC16 和 MUC5AC 的粘蛋白基因和蛋白表达。
与对照剂处理的干眼症相比,VApal 处理的干眼症在第 3 天(P<0.05)和第 7 天(P<0.01)时荧光素染色面积和玫瑰红染色评分均显著降低。VApal 处理后第 1 天(P<0.01)角膜 rMuc4 和结膜 rMuc5AC 显著增加,第 3 天结膜 rMuc16 基因表达增加(P<0.05)。此外,VApal 处理后第 3 天结膜 MUC16 表达显著增加(P<0.05)。
VApal 促进了损伤后大鼠干眼病模型中角膜 rMuc4、结膜 rMuc5AC 和结膜 rMuc16 基因的表达,同时还促进了结膜 MUC16 的表达。这些结果表明,VApal 可改善与泪液产生减少相关的角结膜上皮损伤的疗效。