Department of Medical Genetics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Ocul Pharmacol Ther. 2022 Jan-Feb;38(1):3-32. doi: 10.1089/jop.2021.0067. Epub 2021 Nov 17.
Age-related macular degeneration (AMD) is a major leading cause of irreversible visual impairment in the world with limited therapeutic interventions. Histological, biochemical, genetic, and epidemiological studies strongly implicate dysregulated lipid metabolism in the retinal pigmented epithelium (RPE) in AMD pathobiology. However, effective therapies targeting lipid metabolism still need to be identified and developed for this blinding disease. To test lipid metabolism-targeting therapies, preclinical AMD mouse models are needed to establish therapeutic efficacy and the role of lipid metabolism in the development of AMD-like pathology. In this review, we provide a comprehensive overview of current AMD mouse models available to researchers that could be used to provide preclinical evidence supporting therapies targeting lipid metabolism for AMD. Based on previous studies of AMD mouse models, we discuss strategies to modulate lipid metabolism as well as examples of studies evaluating lipid-targeting therapeutics to restore lipid processing in the RPE. The use of AMD mouse models may lead to worthy lipid-targeting candidate therapies for clinical trials to prevent the blindness caused by AMD.
年龄相关性黄斑变性(AMD)是世界范围内导致不可逆性视力损害的主要原因,目前治疗方法有限。组织学、生化、遗传学和流行病学研究强烈表明,视网膜色素上皮(RPE)中脂质代谢失调与 AMD 的发病机制有关。然而,对于这种致盲性疾病,仍需要确定和开发针对脂质代谢的有效治疗方法。为了测试针对脂质代谢的治疗方法,需要建立临床前 AMD 小鼠模型来验证治疗效果和脂质代谢在 AMD 样病理发生中的作用。在这篇综述中,我们全面概述了现有的可用于研究人员的 AMD 小鼠模型,这些模型可提供支持针对 AMD 进行脂质代谢治疗的临床前证据。基于之前的 AMD 小鼠模型研究,我们讨论了调节脂质代谢的策略以及评估脂质靶向治疗药物以恢复 RPE 中脂质处理的研究实例。AMD 小鼠模型的使用可能会为临床试验带来有价值的脂质靶向候选治疗方法,以预防 AMD 引起的失明。