3讨论 PEDF是由Tombran 等[2]首先在胚胎RPE细胞的条件培养基中发现的具有神经营养作用的蛋白质,其基因位于染色体17p13.1[5,6],与视网膜色素变性常染色体显性位点密切相连。它由RPE细胞分泌产生,贮存于感光细胞基质内[7]。研究表明PEDF在视网膜神经元培养系统能够抑制过氧化氢诱导的细胞凋亡[8];在遗传性视网膜变性鼠模型中可以延长感光细胞的存活时间[3];在去除RPE细胞后,外源性PEDF可以维持正常感光细胞神经元的发育和视紫质的表达[9]。Yabe等[10]证实NF kappaB是PEDF发挥其神经保护作用所必需的信号转导分子,PEDF 通过此途径来维持小脑颗粒细胞神经元的存活,从而诱导其它抗凋亡和/或神经营养因子基因的表达。 我们将外源性PEDF注射入SD鼠玻璃体腔内,连续光照后进行ERG和组织形态学检查,结果表明PEDF组暗视蓝光、暗视白光和明视白光ERG b波振幅与PBS组的相应 b波振幅差别均具有显著性意义,组织形态学结果表明PEDF组的鼠眼ONL得到了较好的保留,从而从功能学和解剖形态学上证实PEDF具有保护受连续光损伤感光细胞活性的作用,同时也表明PEDF可能是在感光细胞受损伤的早期阶段发挥其保护作用。PEDF对锥体细胞的保护作用对维持明视功能特别重要。Sygawara等[11]认为在光损伤鼠模型(1000~2000lx光照条件下),锥体细胞的丧失是杆体细胞丧失间接造成的,因鼠杆体细胞丧失50%多以后锥体细胞的丧失才明显,因此在PEDF组,锥体细胞的挽救可能是杆体细胞保存的间接结果。 目前研究已表明PEDF能够抑制碱性成纤维细胞生长因子(basic fibroblast growth factor, bFGF)的促有丝分裂和促血管生成活性[12,13],是一种非常有效的抗血管生成因子。PEDF对视网膜感光细胞神经元的保护作用以及它的抗血管生成的双重特性[14],必将为视网膜变性疾病的预防和治疗开辟一个全新的领域。其具体作用机制仍有待于进一步研究。
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