CD59a在激光诱导小鼠脉络膜新生血管形成中的作用

Role of CD59a in laser-induced choroidal neovascularization

目的探讨补体调节蛋白CD59a在激光诱导小鼠脉络膜新生血管(choroidal neovascularization,CNV)形成中的作用。方法实验分3组:C57BL/6小鼠对照组、CD59a(-/-)小鼠组、rsCD59a-FC预处理小鼠组。氪红激光光凝诱导小鼠CNV模型,观察上皮-脉络膜-巩膜复合物CNV的发生率;免疫组化检测膜攻击复合物沉积;RT-PCR检测CD59a mRNA表达。结果 C57BL/6小鼠对照组在光凝后第3天、第5天见CD59a mRNA表达下调,分别为60%、30%。CD59a(-/-)小鼠组、rsCD59a-FC预处理小鼠组在光凝后第3天、第5天未见CD59a mRNA表达下调。C57BL/6小鼠见少量膜攻击复合物沉积、CD59a(-/-)小鼠见大量膜攻击复合物沉积、rsCD59a-FC预处理组未见膜攻击复合物沉积。光凝后第5天,C57BL/6小鼠见少量CNV生成;CD59a(-/-)小鼠见大量CNV形成;rsCD59a-FC预处理小鼠未见CNV形成。结论激光诱导小鼠CNV形成过程中,膜攻击复合物起核心作用;CD59a调节补体激活,rsCD59a-FC通过阻断MAC的沉积阻断小鼠CNV的形成;rsCD59a-FC将成为治疗AMD疾病的又一策略。

Objective To study the role of complement CD59a in laser-induced choroidal neovascularization （CNV）. Methods Experiments in three groups： C57BL/6 mice control group, CD59a（-/-）mice group, rsCD59a-FC pretreatment mice group. CNV was induced by laser photocoagulation with the krypton red laser, the inci- dence of epithelium-choroid-sclera CNV were determined by confocal microscopy. RPE-choroid-scleral flat mounts were stained for membrane attack complex （ MAC ）, and RT-PCR analysis was used to examine the expression of CD59a mRNA. Results The expressions of CD59a mRNA at postoperative 3 days, 5 days decreased 50% and 30% in C57BL/5 mice control group, which in CD59a（-/-） mice group and rsCD59a-FC pretreatment mice group unchanged. A few of MAC deposition was observed in CD59a （-/-） mice group, little was in C57BL/6 mice control group, and no MAC staining was observed in rsCD59a-FC pretreatment mice group. At postoperative 5 days, little CNV were induced in C57/BI/5 mice group, many in CD59a（-/-）mice group, and no in CNV were induced in rsCD59a-FC pretreatment mice group. Coneluslon MAC formation plays a central role in the laser-induced CNV, and CD59a plays a crucial role in regula- ting complement activation that driving the development of laser-induced CNV in mice. Administration of rsCD59a-Fc may provide a novel therapeutic alternative to current treatment.