Peiretti Enrico, Dessì Sandra, Mulas Maria F, Abete Claudia, Galantuomo Maria S, Fossarello Maurizio
Department of Surgical Sciences, Eye Clinic, University of Cagliari, Via Ospedale, I-09124 Cagliari, Italy.
Exp Eye Res. 2006 Sep;83(3):536-42. doi: 10.1016/j.exer.2006.02.005. Epub 2006 May 11.
To determine whether the fibrovascular proliferation observed in pterygium, may be, at least in part, mediated by an increased activity of cholesterol metabolism. The correlation between lipid metabolism and rate of growth was studied in human normal conjunctival (NCF) and primary pterygium fibroblasts (PFs) in primary culture. The expression of two proliferation markers (Ki-67 and p53) was evaluated by immunohistochemical staining techniques. Proliferation was evaluated by [(3)H]thymidine incorporation and by immunohistochemical assays. Lipid metabolism was evaluated by (14)C-oleate incorporated into cholesterol esters as well as by oil red O staining. Moreover, the cultures of pterygium fibroblasts were supplemented with two antiproliferative drugs in order to confirm the effective alterations in cholesterol metabolism related to proliferation. Immunohistochemistry of frozen sections from primary pterygium demonstrated an increased staining in Ki-67 and p53 compared with staining observed in normal conjunctiva. A dramatically increased activity of intracellular cholesterol metabolism was demonstrated in pterygium fibroblasts obtained from four different patients. This finding was confirmed by the reduction of cholesterol metabolism in pterygium fibroblasts treated with antiproliferative drugs. Collectively, these data support the hypothesis that alterations of cholesterol metabolism are involved in the development of pterygia. This finding may represent a target of new therapeutic approaches for treatment and prevention of pterygium.
为了确定在翼状胬肉中观察到的纤维血管增殖是否至少部分由胆固醇代谢活性增加介导。在原代培养的人正常结膜(NCF)和原发性翼状胬肉成纤维细胞(PFs)中研究脂质代谢与生长速率之间的相关性。通过免疫组织化学染色技术评估两种增殖标志物(Ki-67和p53)的表达。通过[³H]胸腺嘧啶核苷掺入和免疫组织化学分析评估增殖情况。通过掺入胆固醇酯中的¹⁴C-油酸以及油红O染色评估脂质代谢。此外,为了证实与增殖相关的胆固醇代谢的有效改变,在翼状胬肉成纤维细胞培养物中添加了两种抗增殖药物。原发性翼状胬肉冰冻切片的免疫组织化学显示,与正常结膜中观察到的值相比,Ki-67和p53的染色增加。在来自四名不同患者的翼状胬肉成纤维细胞中,细胞内胆固醇代谢活性显著增加。在用抗增殖药物处理的翼状胬肉成纤维细胞中胆固醇代谢的降低证实了这一发现。总体而言,这些数据支持胆固醇代谢改变参与翼状胬肉发展的假说。这一发现可能代表了治疗和预防翼状胬肉新治疗方法的一个靶点。