Leclercq Bastien, Mejlachowicz Dan, Behar-Cohen Francine
Centre de Recherche des Cordeliers, From Physiopathology of Ocular Diseases to Clinical Development, Sorbonne University, Université de Paris Cité, Inserm, F-75006 Paris, France.
Assistance Publique Hôpitaux de Paris, Ophtalmopole, Cochin Hospital, Université de Paris Cité, F-75015 Paris, France.
Pharmaceutics. 2022 May 6;14(5):998. doi: 10.3390/pharmaceutics14050998.
The eye is formed by tissues and cavities that contain liquids whose compositions are highly regulated to ensure their optical properties and their immune and metabolic functions. The integrity of the ocular barriers, composed of different elements that work in a coordinated fashion, is essential to maintain the ocular homeostasis. Specialized junctions between the cells of different tissues have specific features which guarantee sealing properties and selectively control the passage of drugs from the circulation or the outside into the tissues and within the different ocular compartments. Tissues structure also constitute selective obstacles and pathways for various molecules. Specific transporters control the passage of water, ions, and macromolecules, whilst efflux pumps reject and eliminate toxins, metabolites, or drugs. Ocular barriers, thus, limit the bioavailability of gene therapy products in ocular tissues and cells depending on the route chosen for their administration. On the other hand, ocular barriers allow a real local treatment, with limited systemic side-effects. Understanding the different barriers that limit the accessibility of different types of gene therapy products to the different target cells is a prerequisite for the development of efficient gene delivery systems. This review summarizes actual knowledge on the different ocular barriers that limit the penetration and distribution of gene therapy products using different routes of administration, and it provides a general overview of various methods used to bypass the ocular barriers.
眼睛由含有液体的组织和腔室构成，这些液体的成分受到严格调节，以确保其光学特性以及免疫和代谢功能。由不同元素协同工作构成的眼屏障的完整性，对于维持眼部内环境稳定至关重要。不同组织细胞之间的特化连接具有特定特征，可确保密封特性，并选择性地控制药物从循环系统或外部进入组织以及在不同眼内隔室之间的 passage。组织结构也构成了各种分子的选择性障碍和途径。特定的转运蛋白控制水、离子和大分子的 passage，而外排泵则排出和清除毒素、代谢物或药物。因此，眼屏障会根据基因治疗产品的给药途径限制其在眼组织和细胞中的生物利用度。另一方面，眼屏障允许进行真正的局部治疗，全身副作用有限。了解限制不同类型基因治疗产品进入不同靶细胞的不同屏障，是开发高效基因递送系统的先决条件。本综述总结了关于不同眼屏障的实际知识，这些屏障通过不同给药途径限制基因治疗产品的渗透和分布，并概述了用于绕过眼屏障的各种方法。
