Amann J, Kaven C, Spraul C W, Lang G K, Lang G E
Universitäts-Augenklinik Ulm.
Ophthalmologe. 2000 Nov;97(11):737-41. doi: 10.1007/s003470070020.
The long-acting somatostatin analogue octreotide is used as a therapeutic option for patients with diabetic retinopathy and age-related macular degeneration. Growth factors, such as EGF, bFGF, VEGF, and PDGF, have been implicated in the pathogenesis of these diseases. The aim of this study was to investigate the effect of octreotide on the growth-factor-induced proliferation of bovine retinal pigment epithelial (RPE) cells in vitro.
RPE cells were assayed for proliferation as measured by (3H)-thymidine uptake (ccpm). Bovine RPE cells at passage 3-8 were seeded in a 96-well plate and incubated for a 24-h period with a minimum medium followed by a 24-h incubation with the different growth factors at a concentration of 10 ng/ml with and without 5 x 10(-5) M octreotide. In a different assay the cells were incubated with octreotide at 5 x 10(-10)-5 x 10(-4) M. Afterwards the cells were pulsed with 5 microCi/ml (3H)-thymidine for 12 h, and the incorporated radioactivity was measured on glass fiber filters in a beta-counter (mean +/- SEM ccpm). The Wilcoxon Signed Rank test and the student's t-test were used for statistical analyses.
There was a biphasic effect of octreotide on RPE cell proliferation. Exposure of RPE cells to PDGF (20,225 +/- 3304 ccpm) and bFGF (3441 +/- 539 ccpm) resulted in a significantly higher proliferation compared to control medium (1543 +/- 352 ccpm) (p < 0.05). No difference was found for EGF (2385 +/- 383 ccpm). For VEGF (776 +/- 83 ccpm) a significant reduction in RPE cell proliferation was found (P < 0.05). There was a significant reduction in proliferation of RPE cells with PDGF, bFGF, and EGF in combination with octreotide versus growth factors alone (octreotide in combination with PDGF 308 +/- 82 ccpm, with bFGF 229 +/- 88 ccpm, with EGF 2362 +/- 91 ccpm) (p < 0.005). VEGF in combination with octreotide resulted in a significant inhibition of RPE cell proliferation compared to VEGF alone (p < 0.0005).
The data suggest that there is an inhibitory effect of octreotide on RPE cell proliferation of bovine RPE cells and on the increased proliferation of bovine RPE cells induced by PDGF and bFGF. An enhanced inhibitory effect is found for the combination of octreotide and VEGF.
长效生长抑素类似物奥曲肽被用作糖尿病视网膜病变和年龄相关性黄斑变性患者的一种治疗选择。生长因子，如表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）和血小板衍生生长因子（PDGF），与这些疾病的发病机制有关。本研究的目的是在体外研究奥曲肽对生长因子诱导的牛视网膜色素上皮（RPE）细胞增殖的影响。
通过（3H）-胸腺嘧啶核苷摄取量（每分钟计数，ccpm）来测定RPE细胞的增殖。将传代3至8代的牛RPE细胞接种于96孔板中，先用基础培养基孵育24小时，然后分别用浓度为10 ng/ml的不同生长因子，在有或无5×10（-5）M奥曲肽的情况下再孵育24小时。在另一项实验中，将细胞与浓度为5×10（-10）至5×10（-4）M的奥曲肽一起孵育。之后，用5微居里/毫升的（3H）-胸腺嘧啶核苷脉冲处理细胞12小时，并在β计数器中测定玻璃纤维滤膜上的掺入放射性（平均±标准误，ccpm）。采用Wilcoxon符号秩和检验及学生t检验进行统计学分析。
奥曲肽对RPE细胞增殖具有双相效应。与对照培养基（1543±352 ccpm）相比，RPE细胞暴露于PDGF（20225±3304 ccpm）和bFGF（3441±539 ccpm）时增殖显著增加（p<0.05）。EGF（2385±383 ccpm）组未发现差异。对于VEGF（776±83 ccpm），RPE细胞增殖显著降低（P<0.05）。与单独使用生长因子相比，奥曲肽与PDGF、bFGF和EGF联合使用时，RPE细胞增殖显著降低（奥曲肽与PDGF联合为308±82 ccpm，与bFGF联合为229±88 ccpm，与EGF联合为2362±91 ccpm）（p<0.005）。与单独使用VEGF相比，奥曲肽与VEGF联合使用导致RPE细胞增殖显著抑制（p<0.0005）。
数据表明，奥曲肽对牛RPE细胞的增殖以及PDGF和bFGF诱导的牛RPE细胞增殖增加具有抑制作用。奥曲肽与VEGF联合使用时发现有增强的抑制作用。
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