(4)转录水平调控治疗PVR。转录因子E2F促进细胞生长的某些基因在转录水平上有调控作用,通过阻断E2F的表达来抑制基因转录对治疗增生性疾病具有巨大潜力。Akimoto等[23]将人Tenon囊的成纤维细胞与携带有E2F 的日本凝血病毒的阳离子脂质体(HVJCL)共同培养,通过荧光染色显微镜、RTPCD等方法观察实验结果,表明HVJCL促进外部寡核苷酸转入人成纤维细胞, decoy抑制了cmyc、cdc2等细胞周期相关基因,增生性细胞核抗原和脱氢叶酸盐还原酶等mRNA的共同表达。
4 讨 论
PVR的细胞学基础及发病机制被众多学者广泛关注,机体生长因子的平衡性是关键因素,生长因子与抑制因子组成了一个庞大的系统,各种因子通过特定的途径阻断或抑制PVR的发生过程,从而发挥预防与治疗作用。目前众多因子中PDGF被证明是最有前途的一种抑制因子,如何进一步开发与利用PDGF,还需大量的基础与临床研究。
手术治疗虽然是一种有效的去除PVR增生膜的方法,但是复发率高,并有血眼屏障的破坏、炎症反应重的缺点,仍然不能解决大多数患者最终失明的结果。药物为PVR的治疗提供了广阔的前景,但由于抗细胞代谢增生的药物存在不同程度毒性,至今仍然难以应用于临床。
基因治疗似乎成为治疗PVR的一种有效方法,但PVR的基因治疗还存在很多问题。PVR的基因治疗目前还处于动物实验阶段,PVR基因治疗中所用的启动子在视网膜细胞中表达率难以掌握,而且体外基因转移也是一个重要的研究领域,人视网膜细胞在体外进行长期培养与传代,细胞的生物学特性是否改变仍然值得研究。在PVR的基因治疗研究中,采用最多的是逆转录病毒载体,其安全性一直引起关注。另外,基因治疗过程中,必须要考虑的是引入载体的基因表达能力,是否可调节以及它们对机体的潜在毒副作用。
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