Vertebrate opsins for vision restoration

我们最珍视的感觉，视觉，开始于光传导的过程，这是一个由高度专业化的视网膜感光细胞执行的过程。七种跨膜蛋白负责光捕捉，它们通过进化进化成许多不同的形式。在大多数遗传性致盲疾病中，光感受器细胞会发生变化，失去捕捉光线的能力。为了使失去内源性视蛋白的视网膜恢复活力，有人提出，在这些休眠的光感受器中可以表达简单的单组分微生物视蛋白。这导致了对啮齿动物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光敏感度低，它们在人类中具有潜在的免疫原性，并且它们在高等灵长类动物中难以表达。在这里，我们建议使用专门设计的人类视锥视蛋白系统来治疗视杆细胞营养不良症中残留的视网膜神经元。这些脊椎动物视锥蛋白，包括其调节的离子通道，与针对视锥细胞和神经节细胞的新靶向策略相结合，将绕过与单组分微生物视蛋白相关的缺点，并提供一种高度治疗相关性的失明解决方案，适用于临床。

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.