Vertebrate opsins for vision restoration

用于视力恢复的脊椎动物视蛋白

• 批准号: 391083415
• 负责人: Professor Dr. Stefan Herlitze
• 金额: --
• 依托单位: Lehrstuhl für Allgemeine Zoologie und Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/391083415?language=en
• 关键词: Vertebrate; opsins; vision; restoration

Our most cherished sense, vision, begins with the process of phototransduction, a process performed by the highly specialized photoreceptor cells of the retina. Seven transmembrane proteins are responsible for light capture and they have evolved into many different forms through evolution. In majority of inherited blinding diseases photoreceptor cells are altered losing the ability to capture light. To re-animate retinas that have lost their endogenous opsins it has been suggested that simple one-component microbial opsins can be expressed in these dormant photoreceptors. This has lead to elegant proof-of-concept studies in rodents showing that it is possible to restore visual function. However, the major drawback with these microbial opsin systems is their low light sensitivity, their potential immunogenicity in humans and difficulty of their expression in higher primates. Here, we propose to use human cone opsin systems specifically designed to work in remaining retinal neurons in rod-cone dystrophies. These vertebrate cone opsins including their modulated ion channels in combination with new targeting strategies to cones and ganglion cells will circumvent the shortcomings associated with one-component microbial opsins, and offer a highly therapeutically relevant solution to blindness, applicable in the clinic.

我们最珍贵的感觉，视觉，开始于光传导的过程，这一过程由高度特化的视网膜感光细胞完成。七种跨膜蛋白负责光捕获，并且它们通过进化而进化成许多不同的形式。在大多数遗传性致盲疾病中，感光细胞发生改变，失去捕获光的能力。为了使已经失去内源性视蛋白的视网膜复活，已经提出可以在这些休眠的光感受器中表达简单的单组分微生物视蛋白。这导致了在啮齿动物中进行的优雅的概念验证研究，表明恢复视觉功能是可能的。然而，这些微生物视蛋白系统的主要缺点是它们的低光敏感性、它们在人类中的潜在免疫原性以及它们在高等灵长类动物中表达的困难。在这里，我们建议使用专门设计用于在杆-锥营养不良中剩余的视网膜神经元中工作的人类视锥蛋白系统。这些脊椎动物视锥细胞视蛋白，包括其调节的离子通道，与视锥细胞和神经节细胞的新靶向策略相结合，将避免与单组分微生物视蛋白相关的缺点，并提供高度治疗相关的失明解决方案，适用于临床。