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紫杉醇用于治疗增殖性玻璃体视网膜病变。

Taxol for the treatment of proliferative vitreoretinopathy.

作者信息

van Bockxmeer F M, Martin C E, Thompson D E, Constable I J

出版信息

Invest Ophthalmol Vis Sci. 1985 Aug;26(8):1140-7.

PMID:2862129
Abstract

Proliferative vitreoretinopathy (PVR) results in retinal detachment and visual impairment due to fibroblastic proliferation in the vitreous and subsequent cellular contraction. The authors have used an in vitro model for PVR to evaluate the action of the antineoplastic drug, taxol, on chorioretinal fibroblast proliferation and contractility. Dose response curves obtained show taxol to be a potent inhibitor of both cellular events. Fifty percent inhibition of contraction and proliferation occurred at 2 X 10(-8)M and 3 X 10(-9)M, respectively. On the basis of this pharmacodynamic data, three dosage regimes were chosen to evaluate possible prevention of PVR in an animal model based on the intravitreal injection of cultured fibroblasts. These animals trials show that a single intravitreal dose of either 35 micrograms or 0.5 microgram taxol significantly reduces incidence and extent of PVR. The average grade of vitreoretinal traction at 28 days for 35 micrograms taxol and 250,000 cells was 0.4 (control 1.8); for 35 micrograms taxol and 700,000 cells, 1.0 (control 2.2); and for 0.5 microgram taxol and 250,000 cells, 1.0 (control 2.3). Delayed optic nerve damage was noted with the highest dose used, but a good therapeutic margin may exist. Long-term clinical histopathologic and electrophysiologic studies will be required. The authors conclude from these preliminary studies that taxol holds definite promise for the relief of traction retinal detachment and PVR.

摘要

增殖性玻璃体视网膜病变(PVR)会导致视网膜脱离和视力损害,这是由于玻璃体中的成纤维细胞增殖以及随后的细胞收缩所致。作者使用了一种PVR的体外模型来评估抗肿瘤药物紫杉醇对脉络膜视网膜成纤维细胞增殖和收缩性的作用。所获得的剂量反应曲线表明紫杉醇是这两种细胞事件的有效抑制剂。收缩和增殖的50%抑制分别发生在2×10⁻⁸M和3×10⁻⁹M。基于这些药效学数据,选择了三种给药方案来评估在基于玻璃体内注射培养成纤维细胞的动物模型中预防PVR的可能性。这些动物试验表明,玻璃体内单次注射35微克或0.5微克紫杉醇可显著降低PVR的发生率和程度。对于35微克紫杉醇和250,000个细胞,在28天时玻璃体视网膜牵引的平均等级为0.4(对照组为1.8);对于35微克紫杉醇和700,000个细胞,为1.0(对照组为2.2);对于0.5微克紫杉醇和250,000个细胞,为1.0(对照组为2.3)。在使用的最高剂量下观察到了延迟性视神经损伤,但可能存在良好的治疗窗。需要进行长期的临床、组织病理学和电生理学研究。作者从这些初步研究中得出结论,紫杉醇对于缓解牵引性视网膜脱离和PVR具有明确的前景。

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