选择性PDGF受体酪氨酸激酶抑制剂对兔PVR的治疗作用

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

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。

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.