Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa
Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa
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DOI：
10.1126/science.1190897
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发表时间：
2010-07-23
期刊：
影响因子：
56.9
通讯作者：
Roska, Botond
中科院分区：
文献类型：
--
作者：
Busskamp, Volker;Duebel, Jens;Roska, Botond
色素性视网膜炎指的是一组不同的遗传性疾病，导致无法治愈的失明，影响全球200万人。作为一种常见的病理，杆状感光细胞死亡较早，而光不敏感、形态改变的视锥细胞感光细胞存活时间更长。目前还不清楚这些锥体是否可以进行治疗干预。在这里，我们证明了古生菌卤视紫质在光不敏感的视锥细胞中的表达可以替代自然的光转导级联，并在小鼠视网膜色素变性模型中恢复光敏感性。重新敏感的光感受器激活所有视网膜锥体通路，驱动复杂的视网膜回路功能(包括方向选择性)，激活皮质回路，并调节视觉引导行为。利用人的体外视网膜，我们证明了卤视紫质可以重新激活对光不敏感的人的光感受器。最后，我们确定了具有持续的、对光不敏感的视锥细胞的盲人患者，以进行潜在的基于卤视紫质的治疗。
Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.