Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Int J Mol Sci. 2021 Nov 2;22(21):11877. doi: 10.3390/ijms222111877.
The retina is a light-sensing ocular tissue that sends information to the brain to enable vision. The blood-retinal barrier (BRB) contributes to maintaining homeostasis in the retinal microenvironment by selectively regulating flux of molecules between systemic circulation and the retina. Maintaining such physiological balance is fundamental to visual function by facilitating the delivery of nutrients and oxygen and for protection from blood-borne toxins. The inner BRB (iBRB), composed mostly of inner retinal vasculature, controls substance exchange mainly via transportation processes between (paracellular) and through (transcellular) the retinal microvascular endothelium. Disruption of iBRB, characterized by retinal edema, is observed in many eye diseases and disturbs the physiological quiescence in the retina's extracellular space, resulting in vision loss. Consequently, understanding the mechanisms of iBRB formation, maintenance, and breakdown is pivotal to discovering potential targets to restore function to compromised physiological barriers. These unraveled targets can also inform potential drug delivery strategies across the BRB and the blood-brain barrier into retinas and brain tissues, respectively. This review summarizes mechanistic insights into the development and maintenance of iBRB in health and disease, with a specific focus on the Wnt signaling pathway and its regulatory role in both paracellular and transcellular transport across the retinal vascular endothelium.
视网膜是一种感光眼组织，它将信息发送到大脑，以实现视觉。血视网膜屏障 (BRB) 通过选择性调节全身循环和视网膜之间分子的通量，有助于维持视网膜微环境的内稳态。通过促进营养物质和氧气的输送以及防止血液毒素的侵害，维持这种生理平衡对于视觉功能至关重要。由内视网膜血管组成的内 BRB (iBRB) 主要通过视网膜微血管内皮细胞之间的（细胞旁）和通过（细胞内）运输过程来控制物质交换。许多眼部疾病都会观察到 iBRB 的破坏，其特征是视网膜水肿，破坏了视网膜细胞外空间的生理静止状态，导致视力丧失。因此，了解 iBRB 的形成、维持和破坏的机制对于发现恢复受损生理屏障功能的潜在靶点至关重要。这些被揭示的靶点还可以为跨越 BRB 和血脑屏障进入视网膜和脑组织的潜在药物输送策略提供信息，分别。本综述总结了 iBRB 在健康和疾病中的发育和维持的机制见解，特别关注 Wnt 信号通路及其在视网膜血管内皮细胞的细胞旁和细胞内转运中的调节作用。
