环孢霉素A微球兔眼玻璃体内注射的毒性研究

摘要

目的研究一种新型的嵌段聚酯高分子化合物(ε-己内酯-D，L-丙交酯嵌段共聚物)将环孢霉素A(CsA）包封制备成微球，兔眼玻璃体注射后对视网膜和视功能的毒性。方法　采用10只有色兔，玻璃体注射前行间接检眼镜眼底检查及眼电生理检查(ERG)均正常。含有750μg　CsA的5mg微球以注射用生理盐水混悬，在间接检眼镜观察下注射到每只兔的左眼玻璃体腔中部，同样剂量的空白微球注射到右眼对照眼玻璃体中央。在注射后的不同时间点进行ERG检查。处死动物，摘取眼球对视网膜行组织学检查，并检查眼底至8周。结果　注射后1～2周时，平均的b波明显被抑制(P＜0.05)，最大的暗适应ERG抑制出现在第1周。实验眼与对照眼的b波振幅比率为49.5%。ERG值在第4周基本恢复正常。B波的潜伏值在暗适应条件下为正常。A波振幅值和潜伏值在暗适应条件下实验眼与对照眼没有明显差异。组织学检查显示实验眼与对照眼的视网膜在第6周时没有明显改变。结论　玻璃体内注射可降解微球可以安全地将CsA传递至兔眼的后节段。%ObjectiveTo examine the retinal toxicity of the cyclosporine （CsA） after intravitreal injecton of CsA encapsulated in degradable polymeric microspheres by Poly（-caprolactone-block-D，L-Lactide）（PLCA）．rn Methods Ten pigmented rabbits were used．The rabbit eyes were examined and electroretinagraphy （ERG） was performed preoperatively．A dose of 5mg microspheres that contained 750μg CsA was injected intravitreally to the left eye of each rabbit and the right eye received the same dose of microspheres without CsA．The animals were followed up to 8 weeks post injection by clinical examination and ERG at different times to assess retinal function．The eyes were enucleated for histologic evaluation．rn Results Mean b-wave amplitudes were significantly （P＜0.05，student’s t-test） depressed at weeks 1～2．Maximum occurred at 1 week when scotopic ERG’s showed a 49.5%reduction in b-wave ratio．The ERG’s returned to normal by week 4．The b-wave implicit times under scotopic conditions were normal during this procedure．The a-wave amplitudes and implicit times of scotopic ERG’s showed no marked changes in both experimental and control eyes over the duration of study．In histologic analysis，the retinal layers in both the control and experimental eyes at week 6 were normal without evidence of retinal edema or thinning．rn Conclusions Intravitreal injection of degradable polymeric microspheres in rabbits is a safe method to delivery CsA to the posterior segment of the rabbit eye．