Department of Ophthalmology, Medical Faculty, University of Bonn, Bonn, Germany.
Department of Ophthalmology, Medical Faculty, University of Bonn, Bonn, Germany.
Prog Retin Eye Res. 2022 Sep;90:101065. doi: 10.1016/j.preteyeres.2022.101065. Epub 2022 May 11.
Neurodegenerative retinal diseases are a prime cause of blindness in industrialized countries. In many cases, there are no therapeutic treatments, although they are essential to improve patients' quality of life. A set of disease-causing genes, which primarily affect photoreceptors, has already been identified and is of major interest for developing gene therapies. Nevertheless, depending on the nature and the state of the disease, gene-independent strategies are needed. Various strategies to halt disease progression or maintain function of the retina are under research. These therapeutic interventions include neuroprotection, direct reprogramming of affected photoreceptors, the application of non-coding RNAs, the generation of artificial photoreceptors by optogenetics and cell replacement strategies. During recent years, major breakthroughs have been made such as the first optogenetic application to a blind patient whose visual function partially recovered by targeting retinal ganglion cells. Also, RPE cell transplantation therapies are under clinical investigation and show great promise to improve visual function in blind patients. These cells are generated from human stem cells. Similar therapies for replacing photoreceptors are extensively tested in pre-clinical models. This marks just the start of promising new cures taking advantage of developments in the areas of genetic engineering, optogenetics, and stem-cell research. In this review, we present the recent therapeutic advances of gene-independent approaches that are currently under clinical evaluation. Our main focus is on photoreceptors as these sensory cells are highly vulnerable to degenerative diseases, and are crucial for light detection.
神经退行性视网膜疾病是工业化国家失明的主要原因。尽管基因治疗对于提高患者的生活质量至关重要，但在许多情况下，还没有治疗方法。一组主要影响光感受器的致病基因已经被确定，这对于开发基因治疗具有重要意义。然而，根据疾病的性质和状态，还需要非基因依赖的策略。目前正在研究各种阻止疾病进展或维持视网膜功能的治疗干预措施。这些治疗干预措施包括神经保护、受影响光感受器的直接重编程、非编码 RNA 的应用、光遗传学产生人工光感受器和细胞替代策略。近年来，已经取得了重大突破，例如首例基因治疗应用于一名失明患者，通过靶向视网膜神经节细胞，部分恢复了他的视觉功能。此外，RPE 细胞移植疗法正在进行临床试验，有望改善失明患者的视觉功能。这些细胞是从人类干细胞中产生的。类似的用于替代光感受器的疗法正在临床前模型中进行广泛测试。这仅仅是利用基因工程、光遗传学和干细胞研究领域的发展带来有前途的新疗法的开始。在这篇综述中，我们介绍了目前正在临床评估的非基因依赖方法的最新治疗进展。我们的主要重点是光感受器，因为这些感觉细胞极易受到退行性疾病的影响，对于光检测至关重要。
