Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
College of Medicine, Zhengzhou University, Zhengzhou, 450001, China.
J Transl Med. 2024 Oct 4;22(1):898. doi: 10.1186/s12967-024-05441-y.
Retinal neurovascular unit (NVU) is a multi-cellular structure that consists of the functional coupling between neural tissue and vascular system. Disrupted NVU will result in the occurrence of retinal and choroidal vascular diseases, which are characterized by the development of neovascularization, increased vascular permeability, and inflammation. This pathological entity mainly includes neovascular age-related macular degeneration (neovascular-AMD), diabetic retinopathy (DR) retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Emerging evidences suggest that the angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) signaling pathway is essential for the development of retinal and choroidal vascular. Tie receptors and their downstream pathways play a key role in modulating the vascular development, vascular stability, remodeling and angiogenesis. Angiopoietin 1 (Ang1) is a natural agonist of Tie2 receptor, which can promote vascular stability. On the other hand, angiopoietin 2 (Ang2) is an antagonist of Tie2 receptor that causes vascular instability. Currently, agents targeting the Ang/Tie signaling pathway have been used to inhibit neovascularization and vascular leakage in neovascular-AMD and DR animal models. Particularly, the AKB-9778 and Faricimab have shown promising efficacy in improving visual acuity in patients with neovascular-AMD and DR. These experimental and clinical evidences suggest that activation of Ang/Tie signaling pathway can inhibit the vascular permeability, neovascularization, thereby maintaining the normal function and structure of NVU. This review seeks to introduce the versatile functions and elucidate the modulatory mechanisms of Ang/Tie signaling pathway. Recent pharmacologic therapies targeting this pathway are also elaborated and summarized. Further translation of these findings may afford a new therapeutic strategy from bench to bedside.
视网膜神经血管单元（NVU）是一个多细胞结构，由神经组织和血管系统之间的功能偶联组成。NVU 的破坏会导致视网膜和脉络膜血管疾病的发生，这些疾病的特征是新生血管形成、血管通透性增加和炎症。这种病理实体主要包括新生血管性年龄相关性黄斑变性（新生血管性 AMD）、糖尿病性视网膜病变（DR）、视网膜静脉阻塞（RVO）和早产儿视网膜病变（ROP）。新出现的证据表明，血管生成素/酪氨酸激酶免疫球蛋白和表皮生长因子同源结构域（Ang/Tie）信号通路对于视网膜和脉络膜血管的发育至关重要。Tie 受体及其下游途径在调节血管发育、血管稳定性、重塑和血管生成方面发挥着关键作用。血管生成素 1（Ang1）是 Tie2 受体的天然激动剂，可促进血管稳定性。另一方面，血管生成素 2（Ang2）是 Tie2 受体的拮抗剂，可导致血管不稳定。目前，靶向 Ang/Tie 信号通路的药物已被用于抑制新生血管性 AMD 和 DR 动物模型中的新生血管形成和血管渗漏。特别是，AKB-9778 和 Faricimab 在改善新生血管性 AMD 和 DR 患者的视力方面显示出有希望的疗效。这些实验和临床证据表明，激活 Ang/Tie 信号通路可以抑制血管通透性、新生血管形成，从而维持 NVU 的正常功能和结构。本综述旨在介绍 Ang/Tie 信号通路的多功能性，并阐明其调节机制。还详细阐述和总结了针对该通路的最近药理学治疗方法。这些发现的进一步转化可能为从基础到临床提供一种新的治疗策略。
