The Western Eye Hospital, Imperial College Healthcare NHS Trust (ICHNT), London NW1 5QH, UK.
The Imperial College Ophthalmic Research Group (ICORG), Imperial College, London NW1 5QH, UK.
Int J Mol Sci. 2018 Apr 17;19(4):1218. doi: 10.3390/ijms19041218.
Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma.
青光眼是导致不可逆性视力丧失的主要原因之一,据估计,40 岁以上人群中有 3.5%的人患有该病,到 2040 年,全球将有 1.12 亿人受其影响。受影响患者数量的急剧增加表明,我们需要不断改进诊断和治疗这种疾病的方法。膜联蛋白 A5 是一种 36kDa 的蛋白质,在人类中广泛表达,并在多个领域被研究作为细胞凋亡的指标。该分子与磷脂酰丝氨酸具有高钙依赖性亲和力,磷脂酰丝氨酸是细胞凋亡早期外排在细胞膜外的一种细胞膜磷脂。DARC(检测凋亡的视网膜细胞)项目使用荧光标记的膜联蛋白 A5 来评估青光眼变性,其固有过程是视网膜神经节细胞的凋亡。此外,该项目还对眼部和脑部的神经退行性疾病中的视网膜细胞凋亡进行了研究。在本研究中,我们总结了膜联蛋白 A5 作为细胞凋亡标志物在眼部的应用。我们还介绍了 DARC 项目的进展,从疾病的实验模型中开发了体内视网膜神经节细胞凋亡的实时成像,并确定了神经退行性变及其治疗的机制,这些已应用于首次人体临床试验。DARC 有望成为神经退行性疾病的生物标志物,特别是在新型治疗方法的研究中,也可能成为诊断和监测青光眼的有用工具。