Gene therapy for optic nerve disease
Gene therapy for optic nerve disease
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DOI：
10.1038/sj.eye.6701579
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发表时间：
2004-11-01
期刊：
影响因子：
3.9
通讯作者：
Quigley, HA
中科院分区：
文献类型：
--
作者：
Martin, KRG;Quigley, HA
目的近年来，人们对基因治疗技术在眼部疾病治疗中的潜在应用产生了兴趣。在这篇文章中，我们考虑的视神经疾病是潜在的最适合基因治疗。方法我们讨论了最近在青光眼、视神经炎、Leber’s遗传性视神经病变（LHON）和视神经横断动物模型中成功进行的基因转移实验，并评估了未来使用类似技术治疗人类疾病的可能性。结果通过玻璃体内注射腺相关病毒（AAV），我们在青光眼大鼠模型中实现了高效的视网膜神经节细胞转染。在我们的模型中，我们发现与生理盐水或对照病毒注射相比，aav介导的脑源性神经营养因子基因治疗具有显著的神经保护作用。Guy和他的同事已经成功地使用aav介导的基因疗法来替换人类LHON患者细胞中有缺陷的线粒体酶亚基。基因治疗技术在视神经炎和视神经创伤的动物模型中也显示出前景。结论如果载体不断改进并在人眼中具有良好的耐受性，LHON等单基因缺陷的人类疾病可能很快就会通过基因治疗获得成功。其他视神经疾病，如青光眼，没有单基因缺陷，也可能受益于基因治疗，以提高RGC的存活率。在所有情况下，治疗的风险都需要与潜在的益处相平衡。
Purpose There has been recent interest in the potential use of gene therapy techniques to treat ocular disease. In this article, we consider the optic nerve diseases that are potentially most amenable to gene therapy.Methods We discuss the recent success of gene transfer experiments in animal models of glaucoma, optic neuritis, Leber's hereditary optic neuropathy (LHON), and optic nerve transection, and we assess the possibility of using similar techniques to treat human disease in the future.Results We have achieved highly efficient transfection of retinal ganglion cells in a rat model of glaucoma following a single intravitreal injection of adeno-associated virus (AAV). In our model, we have found that AAV-mediated gene therapy with brain-derived neurotrophic factor has a significant neuroprotective effect compared to saline or control virus injections. Guy and co-workers have successfully used AAV-mediated gene therapy to replace the defective mitochondrial enzyme subunit in cells derived from human patients with LHON. Gene therapy techniques have also shown promise in animal models of optic neuritis and optic nerve trauma.Conclusions Human diseases with single-gene defects such as LHON may soon be treated successfully by gene therapy, assuming that vectors continue to improve and are well tolerated in the human eye. Other optic nerve diseases such as glaucoma that do not have a single-gene defect may also benefit from gene therapy to enhance RGC survival. In all cases, the risks of treatment will need to be balanced against the potential benefits.