School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, China.
Invest Ophthalmol Vis Sci. 2013 Sep 19;54(9):6287-97. doi: 10.1167/iovs.13-12081.
To evaluate the efficacy of osmoprotectants on prevention and treatment of dry eye in a murine model.
Dry eye was induced in mice by using an intelligently controlled environmental system (ICES). Osmoprotectants betaine, L-carnitine, erythritol, or vehicle (PBS) were topically administered to eyes four times daily following two schedules: schedule 1 (modeling prevention): dosing started at the beginning of housing in ICES and lasted for 21 or 35 days; schedule 2 (modeling treatment): dosing started after ICES-housed mice developed dry eye (day 21), continuing until day 35. Treatment efficacy was evaluated for corneal fluorescein staining; corneal epithelial apoptosis by TUNEL and caspase-3 assays; goblet cell numbers by PAS staining; and expression of inflammatory mediators, TNF-α, IL-17, IL-6, or IL-1β by using RT-PCR on days 0, 14, 21, and/or 35.
Compared with vehicle, prophylactic administration of betaine, L-carnitine, or erythritol significantly decreased corneal staining and expression of TNF-α and IL-17 on day 21 (schedule 1). Treatment of mouse dry eye with osmoprotectants significantly reduced corneal staining on day 35 compared with day 21 (schedule 2). Relative to vehicle, L-carnitine treatment of mouse dry eye for 14 days (days 21 to 35) resulted in a significant reduction in corneal staining, number of TUNEL-positive cells, and expression of TNF-α, IL-17, IL-6, or IL-1β, as well as significantly increased the number of goblet cells.
Topical application of betaine, L-carnitine, or erythritol systematically limited progression of environmentally induced dry eye. L-carnitine can also reduce the severity of such dry-eye conditions.
评估渗透调节剂对环境诱导性干眼症小鼠模型的预防和治疗效果。
使用智能环境控制系统（ICES）诱导小鼠干眼症。在两种方案下，每日四次向眼部局部施用渗透调节剂甜菜碱、左旋肉碱、赤藓糖醇或载体（PBS）：方案 1（模型预防）：在 ICES 饲养开始时开始给药，持续 21 或 35 天；方案 2（模型治疗）：在 ICES 饲养的小鼠出现干眼症（第 21 天）后开始给药，持续至第 35 天。通过角膜荧光素染色、TUNEL 和 caspase-3 检测评估角膜上皮细胞凋亡、PAS 染色评估杯状细胞数量，以及在第 0、14、21 和/或 35 天使用 RT-PCR 评估炎症介质 TNF-α、IL-17、IL-6 或 IL-1β的表达。
与载体相比，预防性给予甜菜碱、左旋肉碱或赤藓糖醇可显著降低第 21 天（方案 1）的角膜染色和 TNF-α和 IL-17 的表达。与第 21 天相比，用渗透调节剂治疗小鼠干眼症可显著降低第 35 天的角膜染色（方案 2）。与载体相比，用左旋肉碱治疗 14 天（第 21 天至第 35 天）的干眼症小鼠可显著减少角膜染色、TUNEL 阳性细胞数以及 TNF-α、IL-17、IL-6 或 IL-1β的表达，同时显著增加杯状细胞数量。
局部应用甜菜碱、左旋肉碱或赤藓糖醇可系统性地限制环境诱导性干眼症的进展。左旋肉碱还可以减轻这种干眼症的严重程度。
