Yap Timothy E, Donna Piero, Almonte Melanie T, Cordeiro Maria Francesca
The Western Eye Hospital, Imperial College Healthcare NHS Trust (ICHNT), London NW1 5QH, UK.
The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK.
Cells. 2018 Jun 15;7(6):60. doi: 10.3390/cells7060060.
Monitoring real-time apoptosis in-vivo is an unmet need of neurodegeneration science, both in clinical and research settings. For patients, earlier diagnosis before the onset of symptoms provides a window of time in which to instigate treatment. For researchers, being able to objectively monitor the rates of underlying degenerative processes at a cellular level provides a biomarker with which to test novel therapeutics. The DARC (Detection of Apoptosing Retinal Cells) project has developed a minimally invasive method using fluorescent annexin A5 to detect rates of apoptosis in retinal ganglion cells, the key pathological process in glaucoma. Numerous animal studies have used DARC to show efficacy of novel, pressure-independent treatment strategies in models of glaucoma and other conditions where retinal apoptosis is reported, including Alzheimer’s disease. This may forge exciting new links in the clinical science of treating both cognitive and visual decline. Human trials are now underway, successfully demonstrating the safety and efficacy of the technique to differentiate patients with progressive neurodegeneration from healthy individuals. We review the current perspectives on retinal ganglion cell apoptosis, the way in which this can be imaged, and the exciting advantages that these future methods hold in store.
在临床和研究环境中,实时监测体内细胞凋亡是神经退行性变科学尚未满足的需求。对于患者而言,在症状出现之前进行早期诊断可提供开展治疗的时间窗。对于研究人员来说,能够在细胞水平客观监测潜在退行性过程的速率可为测试新型疗法提供一种生物标志物。DARC(凋亡视网膜细胞检测)项目开发了一种微创方法,利用荧光膜联蛋白A5检测视网膜神经节细胞的凋亡速率,而视网膜神经节细胞凋亡是青光眼的关键病理过程。众多动物研究已使用DARC来证明新型非压力依赖性治疗策略在青光眼模型以及其他有视网膜凋亡报道的病症(包括阿尔茨海默病)中的疗效。这可能会在治疗认知和视力衰退的临床科学中建立令人兴奋的新联系。目前人体试验正在进行中,并已成功证明该技术在区分进行性神经退行性变患者与健康个体方面的安全性和有效性。我们综述了关于视网膜神经节细胞凋亡的当前观点、对其进行成像的方式以及这些未来方法所具有的令人兴奋的优势。