Baldysiak-Figiel Alicja, Jong-Hesse Yvonne D, Lang Gerhard K, Lang Gabriele E
Department of Ophthalmology, University Eye Hospital and Clinic, 89075 Ulm, Germany.
J Cataract Refract Surg. 2005 May;31(5):1059-64. doi: 10.1016/j.jcrs.2004.08.056.
To evaluate whether a synthetic analog of somatostatin, octreotide, has an inhibitory effect on lens epithelial cell (LEC) proliferation induced by basal and basic fibroblast growth factor as well as insulin-like growth factor 1.
Confluent LEC cultures were kept in serum-free defined medium containing [(3)H]-thymidine in the presence of octreotide alone at the concentration range of 10(-7) M to 10(-10) M or in combination with either basic fibroblast growth factor or insulin-like growth factor 1. Additionally, the expression of somatostatin receptors (1-5) in LECs were analyzed by reverse transcription-polymerase chain reaction.
Octreotide decreased the proliferation of human LECs in a dose-dependent manner, exhibiting a maximal inhibitory concentration at 10(-9) M (P<.03). Moreover, octreotide (10(-9) M) potently inhibited basic fibroblast growth factor- and insulin-like growth factor 1-induced bovine lens epithelial cell proliferation (P<.0001). The respective products of all 5 subtypes of somatostatin receptors were found in human LECs and somatostatin receptor type 2 in bovine LECs.
The data show that, depending on the concentration, octreotide is able to decrease proliferative responses of LECs. Moreover, the cell proliferation induced by growth factors was potently inhibited by octreotide. Therefore, octreotide could be a potential drug after cataract surgery in prevention of growth factor-dependent proliferative disorders such as posterior capsule opacification and anterior capsule contraction in diabetic patients.
评估生长抑素的合成类似物奥曲肽是否对由碱性成纤维细胞生长因子、基本成纤维细胞生长因子以及胰岛素样生长因子1诱导的晶状体上皮细胞(LEC)增殖具有抑制作用。
将汇合的LEC培养物置于含有[³H] - 胸腺嘧啶核苷的无血清限定培养基中,单独存在浓度范围为10⁻⁷ M至10⁻¹⁰ M的奥曲肽,或与碱性成纤维细胞生长因子或胰岛素样生长因子1联合使用。此外,通过逆转录 - 聚合酶链反应分析LEC中生长抑素受体(1 - 5)的表达。
奥曲肽以剂量依赖性方式降低人LEC的增殖,在10⁻⁹ M时表现出最大抑制浓度(P <.03)。此外,奥曲肽(10⁻⁹ M)有效抑制碱性成纤维细胞生长因子和胰岛素样生长因子1诱导的牛晶状体上皮细胞增殖(P <.0001)。在人LEC中发现了所有5种生长抑素受体亚型的相应产物,在牛LEC中发现了生长抑素受体2型。
数据表明,根据浓度不同,奥曲肽能够降低LEC的增殖反应。此外,奥曲肽有效抑制生长因子诱导的细胞增殖。因此,奥曲肽可能是白内障手术后预防糖尿病患者中依赖生长因子的增殖性疾病(如后囊膜混浊和前囊膜收缩)的潜在药物。