Xie Mengzhen, Wang Lixiang, Deng Yingping, Ma Ke, Yin Hongbo, Zhang Xiaolan, Xiang Xingye, Tang Jing
Department of Ophthalmology West China Hospital Sichuan University, Chengdu 610041, China.
Beijing Institute of Ophthalmology Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.
J Ophthalmol. 2024 Sep 9;2024:5487973. doi: 10.1155/2024/5487973. eCollection 2024.
Corneal diseases represent 5.1% of all eye defects and are the fourth leading cause of blindness globally. Corneal neovascularization can arise from all conditions of chronic irritation or hypoxia, which disrupts the immune-privileged state of the healthy cornea, increases the risk of rejection after keratoplasty, and leads to opacity. In the past decades, significant progress has been made for neovascular diseases of the retina and choroid, with plenty of drugs getting commercialized. In addition, to overcome the barriers of the short duration and inadequate penetration of conventional formulations of antivascular endothelial growth factor (VEGF), multiple novel drug delivery systems, including adeno-associated virus (AAV)-mediated transfer have gone through the full process of bench-to-bedside translation. Like retina neovascular diseases, corneal neovascularization also suffers from chronicity and a high risk of recurrence, necessitating sustained and efficient delivery across the epithelial barrier to reach deep layers of the corneal stroma. Among the explored methods, adeno-associated virus-mediated delivery of anti-VEGF to treat corneal neovascularization is the most extensively researched and most promising strategy for clinical translation although currently although, it remains predominantly at the preclinical stage. This review comprehensively examines the necessity, benefits, and risks of applying AAV vectors for anti-VEGF drug delivery in corneal vascularization, including its current progress and challenges in clinical translation.
角膜疾病占所有眼部缺陷的5.1%，是全球第四大致盲原因。角膜新生血管可由所有慢性刺激或缺氧情况引起，这会破坏健康角膜的免疫赦免状态，增加角膜移植术后排斥反应的风险，并导致角膜混浊。在过去几十年中，视网膜和脉络膜新生血管疾病取得了重大进展，大量药物已商业化。此外，为了克服抗血管内皮生长因子（VEGF）传统制剂作用时间短和穿透力不足的障碍，多种新型药物递送系统，包括腺相关病毒（AAV）介导的递送，已经完成了从实验室到临床的全过程转化。与视网膜新生血管疾病一样，角膜新生血管也具有慢性和高复发风险，需要持续有效地穿过上皮屏障，到达角膜基质深层。在探索的方法中，腺相关病毒介导的抗VEGF递送治疗角膜新生血管是临床转化研究最广泛、最有前景的策略，尽管目前主要仍处于临床前阶段。本文综述全面探讨了在角膜血管化中应用AAV载体进行抗VEGF药物递送的必要性、益处和风险，包括其目前在临床转化方面的进展和挑战。
