选择性PDGF受体酪氨酸激酶抑制剂对兔PVR的治疗作用

目的　评价一种新的血小板源性生长因子 (platelet derivedgrowthfactor,PDGF)受体酪氨酸激酶抑制剂AG12 95对兔增殖性玻璃体视网膜病变 (proliferativevitreoretinopathy ,PVR)的治疗作用。 方法　兔结膜成纤维细胞 (rabbitconjunctivalfibroblastscells,RCF)培养 ,用MTT分析法检测PDGF AA和 BB以及AG12 95对兔RCF的增殖状况的影响。建立PVR动物模型 ,玻璃体腔内给予AG12 95 ,用牵引性视网膜脱离 (tractionalretinaldetach ment,TRD)的发生率判断药物的体内疗效。眼视网膜电生理检查和HE染色分析药物的毒性。结果　 10 μmol·L-1和 10 0 μmol·L-1两种浓度的AG12 95均可显著抑制由PDGF AA和 BB诱导的成纤维细胞的增生 ,10 0 μmol·L-1AG12 95可减缓兔TRD的发生 ,但其作用仅持续至第 2 1d。在AG12 95治疗组中 ,未发现明显的网膜毒性。结论　PDGF受体酪氨酸激酶抑制剂AG12 95可减缓兔TRD的发生。

Platelet-derived growth factor receptor kinase inhibitor AG1295 and inhibition of experimental proliferative vitreoretinopathy

Objective To determine the effect of tyrphostin AG1295, a selective blocker of platelet derived growth factor (PDGF ) receptor tyrosine kinase (RTK), on proliferative vitreoretinopathy PVR development. Methods The rabbit conjunctival fibroblasts cells (1×10 4) were cultured and MTT method was used to evaluate the effect of PDGF AA and BB as well as AG1295 on RCF proliferation. A rabbit PVR model was constructed and 100?μ mol·L -1 of AG1295 was injected intravitreally. The presence of tractional retinal detachment (TRD) was assessed to evaluate the effect of AG1295 in vivo . Electroretinography and histologic studies were performed after intravitreal injection of AG1295 into the untreated eyes to evaluate toxicity. Results Two concentrations of AG1295 (10?μmol·L -1 an 100?μ mol·L -1 ) significantly inhibited rabbit conjunctival fibroblast cell growth stimulated by PDGF AA or BB in vitro . Development of TRD was significantly reduced with 100?μ mol·L -1 of AG1295 until day 21 ( P < 0.01 ) . No significant histologic or retinal functional damage was found in the AG1295 treated group. Conclusion PDGF receptor specific inhibitor AG1295 can attenuate PVR without significant side effects in rabbits.