Lee Deokho, Tomita Yohei, Negishi Kazuno, Kurihara Toshihide
Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Histol Histopathol. 2025 Jan;40(1):11-20. doi: 10.14670/HH-18-756. Epub 2024 May 3.
Retinal ischemia is a fundamental pathologic condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, age-related macular degeneration, and other eye diseases. Extensive inflammation, redox imbalance, apoptosis, and abnormal vascular formation in retinal ischemia could lead to visual impairments. Developing or finding effective treatments is urgently needed to protect the eye against retinal ischemia and related damage. To address the demand, we have searched for promising therapeutic molecular targets in the eye (e.g., hypoxia-inducible factor [HIF], peroxisome proliferator-activated receptor-alpha [PPARα], and nicotinamide adenine dinucleotide [NAD]), and found that modulations of each molecular target might protect the eye against retinal ischemic damage in terms of complex pathologic mechanisms. In the current article, we review and update the therapeutic evidence of modulation of HIF, PPARα, or NAD and discuss future directions for developing promising drugs based on these molecular targets. This summary urges research to obtain more solid evidence of each molecular target in retinal ischemic diseases.
视网膜缺血是一种与视网膜血管阻塞、青光眼、糖尿病视网膜病变、年龄相关性黄斑变性及其他眼部疾病相关的基本病理状况。视网膜缺血时广泛的炎症、氧化还原失衡、细胞凋亡及异常血管形成可导致视力损害。迫切需要开发或找到有效的治疗方法来保护眼睛免受视网膜缺血及相关损伤。为满足这一需求,我们在眼部寻找有前景的治疗分子靶点(如缺氧诱导因子[HIF]、过氧化物酶体增殖物激活受体α[PPARα]和烟酰胺腺嘌呤二核苷酸[NAD]),并发现对每个分子靶点的调节可能通过复杂的病理机制保护眼睛免受视网膜缺血损伤。在本文中,我们回顾并更新了调节HIF、PPARα或NAD的治疗证据,并讨论了基于这些分子靶点开发有前景药物的未来方向。这一综述促使开展研究以获取视网膜缺血性疾病中每个分子靶点更确凿的证据。