Inserm, UMRS 872, Centre de Recherche des Cordeliers, Paris, France.
Prog Retin Eye Res. 2010 Nov;29(6):443-65. doi: 10.1016/j.preteyeres.2010.04.001. Epub 2010 Apr 14.
Because the eye is protected by ocular barriers but is also easily accessible, direct intravitreous injections of therapeutic proteins allow for specific and targeted treatment of retinal diseases. Low doses of proteins are required in this confined environment and a long time of residency in the vitreous is expected, making the eye the ideal organ for local proteic therapies. Monthly intravitreous injection of Ranibizumab, an anti-VEGF Fab has become the standard of care for patients presenting wet AMD. It has brought the proof of concept that administering proteins into the physiologically low proteic concentration vitreous can be performed safely. Other antibodies, Fab, peptides and growth factors have been shown to exert beneficial effects on animal models when administered within the therapeutic and safe window. To extend the use of such biomolecules in the ophthalmology practice, optimization of treatment regimens and efficacy is required. Basic knowledge remains to be increased on how different proteins/peptides penetrate into the eye and the ocular tissues, distribute in the vitreous, penetrate into the retinal layers and/or cells, are eliminated from the eye or metabolized. This should serve as a basis for designing novel drug delivery systems. The later should be non-or minimally invasive and should allow for a controlled, scalable and sustained release of the therapeutic proteins in the ocular media. This paper reviews the actual knowledge regarding protein delivery for eye diseases and describes novel non-viral gene therapy technologies particularly adapted for this purpose.
由于眼睛受到眼内屏障的保护，但又很容易接近，因此可以直接将治疗性蛋白质注入眼内，从而对视网膜疾病进行特异性和靶向治疗。在这种封闭的环境中，只需低剂量的蛋白质，且预计蛋白质在玻璃体内的驻留时间较长，这使得眼睛成为局部蛋白质治疗的理想器官。每月向眼内注射雷珠单抗（一种抗 VEGF Fab）已成为湿性 AMD 患者的标准治疗方法。它证明了向生理低蛋白浓度的玻璃体内给药可以安全进行的概念。当在治疗和安全窗口内给予其他抗体、Fab、肽和生长因子时，它们在动物模型中显示出有益的效果。为了将此类生物分子在眼科实践中的应用扩展，需要优化治疗方案和疗效。关于不同的蛋白质/肽如何穿透眼睛和眼部组织、在玻璃体内分布、穿透视网膜层和/或细胞、从眼睛中消除或代谢，仍需要增加基本知识。这应该是设计新型药物输送系统的基础。新型药物输送系统应该是非侵入性或最小侵入性的，并且应允许在眼内介质中对治疗性蛋白质进行可控、可扩展和持续的释放。本文综述了有关眼部疾病蛋白质输送的现有知识，并描述了特别为此目的而开发的新型非病毒基因治疗技术。
