Protein delivery for retinal diseases: From basic considerations to clinical applications
Protein delivery for retinal diseases: From basic considerations to clinical applications
复制标题
DOI：
10.1016/j.preteyeres.2010.04.001
复制
发表时间：
2010-11-01
影响因子：
17.8
通讯作者：
Behar-Cohen, F.
中科院分区：
文献类型：
--
作者：
El Sanharawi, M.;Kowalczuk, L.;Behar-Cohen, F.
由于眼睛受到眼部屏障的保护，但也很容易接近，治疗性蛋白质的直接玻璃体内注射允许视网膜疾病的特异性和靶向治疗。在这种受限的环境中需要低剂量的蛋白质，并且预期在玻璃体中停留很长时间，使得眼睛成为局部蛋白质治疗的理想器官。每月玻璃体内注射雷珠单抗（一种抗VEGF Fab）已成为湿性AMD患者的标准治疗。它带来了概念的证据，即可以安全地将蛋白质施用到生理学上低蛋白质浓度的玻璃体中。其他抗体、Fab、肽和生长因子已显示当在治疗和安全窗口内施用时对动物模型发挥有益作用。为了扩展这种生物分子在眼科实践中的使用，需要优化治疗方案和功效。关于不同的蛋白质/肽如何渗透到眼睛和眼组织中、分布在玻璃体中、渗透到视网膜层和/或细胞中、从眼睛中消除或代谢的基础知识仍有待增加。这应该作为设计新型药物输送系统的基础。后者应该是非侵入性或最小侵入性的，并且应该允许治疗性蛋白质在眼介质中的受控、可扩展和持续释放。本文回顾了关于蛋白质递送用于眼部疾病的实际知识，并描述了特别适用于此目的的新型非病毒基因治疗技术。(C)2010年由Elsevier Ltd.出版
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. (C) 2010 Published by Elsevier Ltd.