Chen Wensheng, Zhao Kanxing, Li Xiaorong, Yoshitomi Takeshi
Tianjin Medical University Eye Center, Tianjin, China.
Cornea. 2007 Oct;26(9):1101-6. doi: 10.1097/ICO.0b013e318123771e.
The objective of this study was to examine the epithelial stem cell proliferation kinetics in a rat model with keratoconjunctivitis sicca (KCS).
Wistar rats received a daily injection of 5-bromo-2-deoxyuridine (BrdU) at a dose of 5 mg/100 g of body weight for 2 weeks. Dry eye was induced in 2 groups of rats by subcutaneous injection of scopolamine and placed in a desiccating environment: The first group received dry eye treatment at the beginning of BrdU labeling for 2 weeks; the second group received dry eye treatment after BrdU labeling for 4 weeks. Rats receiving no dry eye treatment were used as controls. Aqueous tear production, tear clearance, and corneal barrier function of dry eye rats were compared with those of control rats. Ocular epithelial morphology and goblet cell density were also evaluated in histologic sections. One month after BrdU injection, epithelial stem cell proliferation kinetics was assessed by BrdU labeling.
Significant decreases in tear fluid secretion and tear clearance were noted in rats 5 days after dry eye treatment, with significantly increased corneal carboxy fluorescein uptake. Changes in ocular surface epithelial morphology and significantly reduced density of conjunctival goblet cells were found in dry eye groups. The number of conjunctival BrdU label-retaining cells in the rats with dry eye was significantly decreased compared with control rats (P < 0.01 for both groups). Furthermore, BrdU labeling in the before dry eye induction group showed more label-retaining basal cells in the conjunctiva than labeling in the dry eye state group (P < 0.01).
Experimentally induced KCS in rats causes significant modification of epithelial stem cell proliferation kinetics in conjunctiva. The modification of epithelial stem cell proliferation kinetics in conjunctiva may play a crucial role in the development of KCS and may be a therapeutic target for this condition.
本研究的目的是在大鼠干眼症（KCS）模型中检测上皮干细胞增殖动力学。
Wistar大鼠每天接受剂量为5mg/100g体重的5-溴-2-脱氧尿苷（BrdU）注射，持续2周。通过皮下注射东莨菪碱在2组大鼠中诱导干眼，并将其置于干燥环境中：第一组在BrdU标记开始时接受干眼治疗2周；第二组在BrdU标记4周后接受干眼治疗。未接受干眼治疗的大鼠用作对照。将干眼大鼠的泪液分泌、泪液清除和角膜屏障功能与对照大鼠进行比较。还在组织学切片中评估眼表上皮形态和杯状细胞密度。BrdU注射1个月后，通过BrdU标记评估上皮干细胞增殖动力学。
干眼治疗5天后，大鼠泪液分泌和泪液清除显著减少，角膜羧基荧光素摄取显著增加。在干眼组中发现眼表上皮形态改变和结膜杯状细胞密度显著降低。与对照大鼠相比，干眼大鼠结膜中BrdU标记保留细胞的数量显著减少（两组均P<0.01）。此外，干眼诱导前组的BrdU标记显示结膜中保留标记的基底细胞比干眼状态组更多（P<0.01）。
实验诱导的大鼠KCS导致结膜上皮干细胞增殖动力学的显著改变。结膜上皮干细胞增殖动力学的改变可能在KCS的发展中起关键作用，并且可能是这种病症的治疗靶点。
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