Kim Soo-Young, Qian Haohua
Department of Pharmaceutics, Department of Biology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Center for Nanomedicine, Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University of Medicine, Baltimore, MD, 21287, USA.
Ann Eye Sci. 2022 Mar 15;7. doi: 10.21037/aes-21-25.
In this review, non-transgenic models of age-related macular degeneration (AMD) are discussed, with focuses on murine retinal degeneration induced by sodium iodate and lipid peroxide (HpODE) as preclinical study platforms.
AMD is the most common cause of vision loss in a world with an increasingly aging population. The major phenotypes of early and intermediate AMD are increased drusen and autofluorescence, Müller glia activation, infiltrated subretinal microglia and inward moving retinal pigment epithelium cells. Intermediate AMD may progress to advanced AMD, characterized by geography atrophy and/or choroidal neovascularization. Various transgenic and non-transgenic animal models related to retinal degeneration have been generated to investigate AMD pathogenesis and pathobiology, and have been widely used as potential therapeutic evaluation platforms.
Two retinal degeneration murine models induced by sodium iodate and HpODE are described. Distinct pathological features and procedures of these two models are compared. In addition, practical protocol and material preparation and assessment methods are elaborated.
Retina degeneration induced by sodium iodate and HpODE in mouse eye resembles many clinical aspects of human AMD and complimentary to the existent other animal models. However, standardization of procedure and assessment protocols is needed for preclinical studies. Further studies of HpODE on different routes, doses and species will be valuable for the future extensive use. Despite many merits of murine studies, differences between murine and human should be always considered.
在本综述中,将讨论年龄相关性黄斑变性(AMD)的非转基因模型,重点关注由碘酸钠和脂质过氧化物(HpODE)诱导的小鼠视网膜变性,作为临床前研究平台。
在人口老龄化日益严重的世界中,AMD是导致视力丧失的最常见原因。早期和中期AMD的主要表型为玻璃膜疣增加和自发荧光增强、穆勒胶质细胞活化、视网膜下小胶质细胞浸润以及视网膜色素上皮细胞向内迁移。中期AMD可能进展为晚期AMD,其特征为地图样萎缩和/或脉络膜新生血管形成。已经建立了各种与视网膜变性相关的转基因和非转基因动物模型来研究AMD的发病机制和病理生物学,并已广泛用作潜在的治疗评估平台。
描述了由碘酸钠和HpODE诱导的两种视网膜变性小鼠模型。比较了这两种模型不同的病理特征和操作过程。此外,还阐述了实际操作方案、材料准备和评估方法。
碘酸钠和HpODE诱导的小鼠视网膜变性与人类AMD的许多临床特征相似,并且对现有的其他动物模型具有补充作用。然而,临床前研究需要操作和评估方案的标准化。进一步研究HpODE在不同给药途径、剂量和物种上的作用,对于其未来的广泛应用将具有重要价值。尽管小鼠研究有许多优点,但始终应考虑小鼠与人类之间的差异。