Kirpichnikov M P, Ostrovskiy M A
Lomonosov Moscow State University, Faculty of Biology, 1 str. 12 Leninskie Gory, Moscow, Russian Federation, 119234; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow, Russian Federation, 117997.
Lomonosov Moscow State University, Faculty of Biology, 1 str. 12 Leninskie Gory, Moscow, Russian Federation, 119234; Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygina St., Moscow, Russian Federation, 119334.
Vestn Oftalmol. 2015 May-Jun;131(3):99-111. doi: 10.17116/oftalma2015131399-111.
This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity. The experience with gene therapy came in very useful for optogenetics. However, unlike gene therapy, which is aimed at repairing damaged genes or replacing them with healthy ones, optogenetics is focused on protein genes delivery for further molecular control of the cell. In retina, the loss of photoreceptors is not necessarily followed by neuronal loss (at least ganglion cells remain intact), which determines the practicability of prosthetic treatment. Clinical trials can now be considered, owing to the first successful conversion of ganglion cells of mouse degenerative retinas into artificial photoreceptive cells with ON and OFF receptive fields, which is crucial for spatial vision. The following issues are reviewed here in detail: 1. Choice of cell targets within the degenerative retina. 2. Strategy of utilizing the existing light-sensitive agents and development of new optogenetic tools. 3. Gene delivery and expression in retinal cells. 4. Methods of evaluating the treatment success. 5. Selection criteria for optogenetic prosthetics. The conclusion discusses currently unsolved problems and prospects for optogenetic approaches to retinal prosthetics.
这是一篇关于眼科和视觉生理学领域基于光遗传学的研究现状的综述。光遗传学采用了一种跨学科方法，融合了基因工程、光学和生理学。它涉及在非常特定的视网膜细胞中外源表达一种光激活蛋白，从而能够调节（刺激或抑制）其生理活动。基因治疗的经验对光遗传学非常有用。然而，与旨在修复受损基因或用健康基因替代它们的基因治疗不同，光遗传学专注于蛋白质基因的递送，以便对细胞进行进一步的分子控制。在视网膜中，光感受器的丧失不一定会导致神经元丧失（至少神经节细胞保持完整），这决定了假体治疗的可行性。由于首次成功地将小鼠退化视网膜的神经节细胞转化为具有开和关感受野的人工光感受器细胞，这对空间视觉至关重要，现在可以考虑进行临床试验。本文将详细综述以下问题：1. 退化视网膜内细胞靶点的选择。2. 利用现有光敏剂的策略和新光遗传学工具的开发。3. 视网膜细胞中的基因递送和表达。4. 评估治疗成功的方法。5. 光遗传学假体的选择标准。结论部分讨论了目前尚未解决的问题以及光遗传学方法用于视网膜假体的前景。
