Ozcura Fatih, Dündar Sema Oruç, Cetin Emel Dikicioğlu, Beder Nahit, Dündar Mehmet
Department of Ophthalmology, Dumlupinar University School of Medicine, Kutahya, Turkey.
Int J Ophthalmol. 2012;5(1):64-8. doi: 10.3980/j.issn.2222-3959.2012.01.13. Epub 2012 Feb 18.
To investigate the effects of estrogen replacement therapy (ERT) on apoptosis and vascular endothelial growth factor (VEGF) expression in ocular surface in an experimental rat model.
Forty female, Wistar rats were randomized in 4 groups in the study. Subcutaneous ERT (17β-estradiol, 10µg/kg/day) was administered to the first group without ovariectomy and to the second group with ovariectomy for three months. Third group had only ovariectomy and fourth group had sham operation. All rats were sacrificed in estrous cycles determined by vaginal smear test and their right eyes were enucleated at the end of the third month. Enucleated eyes were analyzed by immunohistochemical method for expressions of caspase-3, bcl-2, VEGF and TUNEL assay.
Caspase-3 expression of conjunctival epithelium was significantly higher in group 3 than group 1 (P=0.005), and group 2 (P=0.007). TUNEL score of conjunctival epithelium was significantly higher in group 3 than group1 (P=0.006). TUNEL score of corneal epithelium was significantly higher in group 3 than group 2 (P=0.012), and group 4 (P=0.002). There was no significant difference between groups in that bcl-2 and VEGF expressions.
We determined increased apoptosis in ocular surface epithelial cells in ovariectomized rats. ERT and endogen estrogen decreased the apoptosis, and did not result in difference in VEGF expression between the groups. Estrogen may be beneficial for the treatment of apoptosis-mediated ocular surface disorders such as dry eye. Further studies are needed on this subject for a better understanding of the role of estrogen and to provide a new insight for treatment and prevention of apoptosis-mediated ocular surface disorders.
在实验性大鼠模型中研究雌激素替代疗法(ERT)对眼表细胞凋亡及血管内皮生长因子(VEGF)表达的影响。
40只雌性Wistar大鼠随机分为4组。第一组未行卵巢切除术,皮下给予ERT(17β - 雌二醇,10μg/kg/天);第二组行卵巢切除术后皮下给予ERT,持续三个月。第三组仅行卵巢切除术,第四组行假手术。通过阴道涂片试验确定所有大鼠处于动情周期时将其处死,在第三个月末摘除其右眼。对摘除的眼球进行免疫组织化学分析,检测半胱天冬酶 - 3、bcl - 2、VEGF的表达,并进行TUNEL检测。
第三组结膜上皮细胞的半胱天冬酶 - 3表达显著高于第一组(P = 0.005)和第二组(P = 0.007)。第三组结膜上皮细胞的TUNEL评分显著高于第一组(P = 0.006)。第三组角膜上皮细胞的TUNEL评分显著高于第二组(P = 0.012)和第四组(P = 0.002)。各组之间bcl - 2和VEGF表达无显著差异。
我们发现去卵巢大鼠眼表上皮细胞凋亡增加。ERT和内源性雌激素可减少细胞凋亡,且各组之间VEGF表达无差异。雌激素可能有助于治疗如干眼等由细胞凋亡介导的眼表疾病。对此主题还需要进一步研究,以更好地理解雌激素的作用,并为治疗和预防由细胞凋亡介导的眼表疾病提供新的见解。