Degenerative retinal disorders are a diverse family of diseases commonly leading to irreversible photoreceptor death, while leaving the inner retina relatively intact. Over recent years, innovative gene replacement therapies aiming to halt the progression of certain inherited retinal disorders have made their way into clinics. By rendering surviving retinal neurons light sensitive optogenetic gene therapy now offers a feasible treatment option that can restore lost vision, even in late disease stages and widely independent of the underlying cause of degeneration.

Since proof-of-concept almost fifteen years ago, this field has rapidly evolved and a detailed first report on a treated patient has recently been published. In this article, we provide a review of optogenetic approaches for vision restoration. We discuss the currently available optogenetic tools and their relative advantages and disadvantages. Possible cellular targets will be discussed and we will address the question how retinal remodelling may affect the choice of the target and to what extent it may limit the outcomes of optogenetic vision restoration. Finally, we will analyse the evidence for and against optogenetic tool mediated toxicity and will discuss the challenges associated with clinical translation of this promising therapeutic concept.

退行性视网膜疾病是多种多样的疾病，通常会导致不可逆的光感受器死亡，同时使内部视网膜相对完好。近年来，旨在阻止某些遗传性视网膜疾病进展的创新基因替代疗法已进入临床。通过渲染幸存的视网膜神经元，光敏光遗传学基因疗法现在提供了一种可行的治疗选择，即使在疾病晚期并且广泛独立于退化的根本原因，也可以恢复丧失的视力。

自大约 15 年前的概念验证以来，该领域发展迅速，最近发表了一份关于接受治疗的患者的详细第一份报告。在这篇文章中，我们回顾了视力恢复的光遗传学方法。我们讨论了当前可用的光遗传学工具及其相对优缺点。将讨论可能的细胞目标，我们将解决视网膜重塑如何影响目标选择以及它可能在多大程度上限制光遗传学视力恢复结果的问题。最后，我们将分析支持和反对光遗传学工具介导的毒性的证据，并将讨论与这一有前途的治疗概念的临床转化相关的挑战。