Nommiste Britta, Fynes Kate, Tovell Victoria E, Ramsden Conor, da Cruz Lyndon, Coffey Peter
Institute of Ophthalmology, London, United Kingdom.
Institute of Ophthalmology, London, United Kingdom; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
Prog Brain Res. 2017;231:225-244. doi: 10.1016/bs.pbr.2017.03.003. Epub 2017 May 19.
Age-related macular degeneration remains the most common cause of blindness in the western world, severely comprising patients' and carers' quality of life and presenting a great cost to the healthcare system. As the disease progresses, the retinal pigmented epithelium (RPE) layer at the back of the eye degenerates, contributing to a series of events resulting in visual impairment. The easy accessibility of the eye has allowed for in-depth study of disease progression in patients, while in vivo studies have facilitated investigations into healthy and diseased RPE. Consequently, a number of research groups are examining different approaches for the replacement of RPE cells in age-related macular degeneration (AMD) patients. This chapter examines some of these initial proof-of-principle studies and goes on to review the use of pluripotent stem cells as a source for RPE replacement in a number of current AMD clinical trials. Finally, we consider just some of the regulatory and manufacturing challenges presented in taking a promising AMD treatment from the research bench into clinical trials in patients, and how to mitigate potential risks early in process development.
年龄相关性黄斑变性仍然是西方世界失明的最常见原因，严重影响患者及其护理人员的生活质量，并给医疗保健系统带来巨大成本。随着疾病的进展，眼睛后部的视网膜色素上皮（RPE）层会退化，引发一系列导致视力受损的事件。眼睛易于接近，便于深入研究患者的疾病进展，而体内研究则有助于对健康和患病的RPE进行调查。因此，一些研究小组正在研究在年龄相关性黄斑变性（AMD）患者中替代RPE细胞的不同方法。本章将探讨其中一些初步的原理验证研究，并继续回顾在当前一些AMD临床试验中使用多能干细胞作为RPE替代来源的情况。最后，我们仅考虑将一种有前景的AMD治疗方法从研究台推进到患者临床试验中所面临的一些监管和生产挑战，以及如何在工艺开发早期减轻潜在风险。
