Borchert Grace A, Shamsnajafabadi Hoda, Ng Benjamin W J, Xue Kanmin, De Silva Samantha R, Downes Susan M, MacLaren Robert E, Cehajic-Kapetanovic Jasmina
Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Front Neurosci. 2024 Jul 1;18:1415575. doi: 10.3389/fnins.2024.1415575. eCollection 2024.
Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch's membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting light-sensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors.
随着人口老龄化，年龄相关性黄斑变性（AMD）日益成为公共卫生问题，并且它是发达国家失明的主要原因，影响55岁以上的人群。AMD影响黄斑区的视网膜色素上皮（RPE）和布鲁赫膜，导致继发性光感受器变性并最终丧失中心视力。晚期AMD分为两种形式：新生血管性AMD和地图状萎缩（GA）。GA约占晚期AMD的60%，一直是最难治疗的亚型。最近的进展包括批准了新的玻璃体内给药疗法，即pegcetacoplan（Syfovre）和avacincaptad pegol（Iveric Bio），它们分别靶向补体因子C3和C5，减缓萎缩区域的扩大速度。然而，目前尚无治疗方法可逆转与GA相关的中心视力丧失。光遗传学可能通过赋予存活的内层视网膜（即视网膜神经节细胞或双极细胞）光敏感性，为挽救GA患者的视觉功能提供一种策略。它利用内层视网膜的残余结构沿视觉通路传递视觉刺激，同时有多种光敏蛋白可供考虑。在此，我们综述GA的解剖学变化，讨论临床前模型中不同靶细胞光遗传学治疗传感器的适用性，并考虑治疗载体不同给药途径的优缺点。
