The human visual cortex responds to gene therapy-mediated recovery of retinal function
The human visual cortex responds to gene therapy-mediated recovery of retinal function
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DOI：
10.1172/jci57377
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发表时间：
2011-06-01
影响因子：
15.9
通讯作者：
Bennett, Jean
中科院分区：
文献类型：
--
作者：
Ashtari, Manzar;Cyckowski, Laura L.;Bennett, Jean
Leber先天性黑蒙（LCA）是一种罕见的退行性眼病，与至少14个基因的突变有关。最近在患有LCA 2的患者中进行的基因治疗试验表明，视网膜下注射携带该基因的正常cDNA（AAV 2-hRPE 65 v2）的acieno-associated virus（AAV）可以显著改善视力。然而，长期感觉剥夺后视觉皮层对视网膜功能恢复的反应仍不清楚。在此，在8岁、9岁和35岁时接受治疗的3名基因治疗试验受试者在单侧注射AAV 2-hRPE 6Sv 2的2年内进行了功能性MRI。与未治疗的眼睛相比，所有受试者暴露于治疗后对高对比度和中等对比度刺激的皮质激活增加。此外，我们观察到治疗眼的视野图和皮质激活分布之间的相关性。这些数据表明，尽管有严重和长期的视觉障碍，治疗的LCA 2患者有完整的和反应性的视觉通路。此外，这些数据表明，基因治疗不仅导致持续和改善的视觉能力，而且还增强了对比敏感度。
Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial in patients with LCA2, who have mutations in RPE65, demonstrated that subretinal injection of an acieno-associated virus (AAV) carrying the normal cDNA of that gene (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation. Here, 3 of the gene therapy trial subjects, treated at ages 8, 9, and 35 years, underwent functional MRI within 2 years of unilateral injection of AAV2-hRPE6Sv2. All subjects showed increased cortical activation in response to high- and medium-contrast stimuli after exposure to the treated compared with the untreated eye. Furthermore, we observed a correlation between the visual field maps and the distribution of cortical activations for the treated eyes. These data suggest that despite severe and long-term visual impairment, treated LCA2 patients have intact and responsive visual pathways. In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity.