年龄相关性黄斑变性的潜在治疗靶点:核选择

IF 18.6 1区 医学 Q1 OPHTHALMOLOGY Progress in Retinal and Eye Research Pub Date : 2023-05-01 DOI:10.1016/j.preteyeres.2022.101130
Mayur Choudhary , Goldis Malek
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引用次数: 3

摘要

核受体是人类基因组中最大的转录因子家族,其功能和活性通常集中在其在内分泌器官中充当类固醇和激素传感器的能力上。然而,在发育和衰老过程中,它们负责一系列不同的生理功能,包括细胞稳态和代谢。尽管眼睛不是传统的内分泌器官,但最近的研究表明,整个后极细胞中的核受体表达水平很高。这些发现促使人们对研究这些转录因子在眼睛中作为年龄和眼部疾病,特别是年龄相关性黄斑变性(AMD)的函数的作用产生了兴趣。作为老年人视力障碍的主要原因,鉴于85%以上的AMD患者缺乏治疗选择,确定可能作为AMD治疗目标的信号通路至关重要。在此,我们回顾了这一相对较新的领域和支持眼睛是第二内分泌器官这一假设的最新发现,其中核受体是AMD易感细胞(包括视网膜色素上皮和脉络膜内皮细胞)生物学过程的基石,并讨论了靶向这些受体治疗AMD的潜力。
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Potential therapeutic targets for age-related macular degeneration: The nuclear option

The functions and activities of nuclear receptors, the largest family of transcription factors in the human genome, have classically focused on their ability to act as steroid and hormone sensors in endocrine organs. However, they are responsible for a diverse array of physiological functions, including cellular homeostasis and metabolism, during development and aging. Though the eye is not a traditional endocrine organ, recent studies have revealed high expression levels of nuclear receptors in cells throughout the posterior pole. These findings have precipitated an interest in investigating the role of these transcription factors in the eye as a function of age and ocular disease, in particular age-related macular degeneration (AMD). As the leading cause of vision impairment in the elderly, identifying signaling pathways that may be targeted for AMD therapy is of great importance, given the lack of therapeutic options for over 85% of patients with this disease. Herein we review this relatively new field and recent findings supporting the hypothesis that the eye is a secondary endocrine organ, in which nuclear receptors serve as the bedrock for biological processes in cells vulnerable in AMD, including retinal pigment epithelial and choroidal endothelial cells, and discuss the therapeutic potential of targeting these receptors for AMD.

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来源期刊
CiteScore
34.10
自引率
5.10%
发文量
78
期刊介绍: Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists. The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.
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