Kon C H, Occleston N L, Foss A, Sheridan C, Aylward G W, Khaw P T
Department of Pathology, Institute of Ophthalmology, London.
Br J Ophthalmol. 1998 May;82(5):554-60. doi: 10.1136/bjo.82.5.554.
To investigate the effects of single, short-term (5 or 30 minutes) exposures to thiotepa or 5-fluorouracil (5-FU) on collagen lattice contraction and retinal pigment epithelial (RPE) cell proliferation.
For collagen contraction studies, RPE cells seeded into free floating type I collagen lattices were exposed to single 5 or 30 minute treatments with thiotepa (0.06-4 mg/ml), or 5-FU (0.25-25 mg/ml), or phosphate buffered saline alone as a control. For proliferation studies, RPE cell monolayers were similarly exposed to these agents. The degree of contraction, effects on cell number, and viability were determined up to 14 days after treatment.
Contraction of collagen lattices containing RPE cells and proliferation of RPE cells were significantly inhibited (p < 0.05) by thiotepa and 5-FU at concentrations above 0.06 mg/ml and 0.25 mg/ml respectively (for both 5 and 30 minute treatments), compared with controls. Cell death did not occur except for exposure of the RPE cells in collagen lattices to the highest concentration of thiotepa (4 mg/ml).
It was concluded that single 5 or 30 minute exposures to thiotepa or 5-FU significantly inhibited collagen contraction and the proliferation of RPE cells. These findings suggest that short, single, non-toxic exposures to thiotepa or 5-FU which can be reproduced clinically may be useful in the modulation of proliferative vitreoretinopathy.
研究硫替派或5-氟尿嘧啶（5-FU）单次短期（5或30分钟）暴露对胶原晶格收缩和视网膜色素上皮（RPE）细胞增殖的影响。
对于胶原收缩研究，将接种到游离漂浮的I型胶原晶格中的RPE细胞分别用硫替派（0.06 - 4mg/ml）、5-FU（0.25 - 25mg/ml）单次处理5或30分钟，或仅用磷酸盐缓冲盐水作为对照。对于增殖研究，RPE细胞单层同样暴露于这些试剂。在处理后长达14天测定收缩程度、对细胞数量的影响和活力。
与对照组相比，硫替派和5-FU在浓度分别高于0.06mg/ml和0.25mg/ml时（5分钟和30分钟处理均如此），显著抑制了含有RPE细胞的胶原晶格收缩和RPE细胞增殖（p < 0.05）。除了胶原晶格中的RPE细胞暴露于最高浓度的硫替派（4mg/ml）外，未发生细胞死亡。
得出结论，硫替派或5-FU单次5或30分钟暴露显著抑制了胶原收缩和RPE细胞增殖。这些发现表明，临床上可重复的硫替派或5-FU单次短期无毒暴露可能有助于调节增殖性玻璃体视网膜病变。
