Night vision restored in days after decades of congenital blindness.
Night vision restored in days after decades of congenital blindness.
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DOI：
10.1016/j.isci.2022.105274
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发表时间：
2022-10-21
期刊：
影响因子：
5.8
通讯作者：
Boye, Shannon E
中科院分区：
文献类型：
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作者：
Jacobson, Samuel G;Cideciyan, Artur V;Ho, Allen C;Roman, Alejandro J;Wu, Vivian;Garafalo, Alexandra V;Sumaroka, Alexander;Krishnan, Arun K;Swider, Malgorzata;Mascio, Abraham A;Kay, Christine N;Yoon, Dan;Fujita, Kenji P;Boye, Sanford L;Peshenko, Igor V;Dizhoor, Alexander M;Boye, Shannon E
视觉向大脑发出的信号始于视网膜光转导级联，它将环境中的可见光转化为化学变化。当突变使光转导级联蛋白失活时，就会导致视力障碍。Leber先天性黑色素是一种严重的单基因遗传性失明，由GUCY2D基因突变引起，导致光信号转导的第二信使环状GMP的产生出现分子缺陷。我们研究了两名正在接受基因增强治疗的GUCY2D-LCA患者。两名患者在干预前都有较大的视杆感受器夜视功能缺陷。在治疗的几天内，两名患者的视杆视力都发生了戏剧性的变化；这些高反应患者的视觉功能和功能视力的改善达到了3log10单位(1000倍)，接近健康的视杆视力。因此，从视网膜光感受器到视觉皮质和行为的复杂分子通路的快速激活在患者身上是可能的，即使在被禁用和休眠数十年后也是可能的。光传导，光感受器中的生化级联，启动视觉先天性失明可能是由于缺陷的光传导(GUCY2D基因突变)GUCY2D基因治疗(低剂量)在治疗后几个月提示一些疗效高剂量治疗现在显示出日间夜间(杆)视力改善的对数单位临床遗传学；健康科学；医学
Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the GUCY2D gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction. We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had large deficits in rod photoreceptor-based night vision before intervention. Within days of therapy, rod vision in both patients changed dramatically; improvements in visual function and functional vision in these hyper-responding patients reached more than 3 log10 units (1000-fold), nearing healthy rod vision. Quick activation of the complex molecular pathways from retinal photoreceptor to visual cortex and behavior is thus possible in patients even after being disabled and dormant for decades. Phototransduction, the biochemical cascade in photoreceptors, initiates vision Congenital blindness can be due to defective phototransduction (GUCY2D gene mutations) GUCY2D gene therapy (low dose) suggested some efficacy after months post-treatment Higher dose therapy now shows log units of improved night (rod) vision over days Clinical genetics; Health sciences; Medicine