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脉络膜内皮细胞转录组分析将雄激素受体作用与中心性浆液性脉络膜视网膜病变联系起来。

Transcriptome Analysis of Choroidal Endothelium Links Androgen Receptor Role to Central Serous Chorioretinopathy.

机构信息

Department of Ophthalmology, University of Bonn, Bonn, Germany.

Department of Ophthalmology, Charité University Hospital Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

出版信息

Eur J Ophthalmol. 2024 Sep;34(5):1532-1540. doi: 10.1177/11206721241226735. Epub 2024 Jan 24.

Abstract

BACKGROUND

Central Serous Chorioretinopathy (CSCR) manifests as fluid accumulation between the neurosensory retina and the retinal pigment epithelium (RPE). Elevated levels of steroid hormones have been implicated in CSCR pathogenesis. This investigation aims to delineate the gene expression patterns of CSCR-associated risk and steroid receptors across human choroidal cell types and RPE cells to discern potential underlying mechanisms.

METHODS

This study utilized a comprehensive query of transcriptomic data derived from non-pathological human choroid and RPE cells.

FINDINGS

CSCR-associated genes such as , , and others are predominantly expressed in the choroidal endothelium as opposed to the RPE. The androgen receptor, encoded by the gene, demonstrates heightened expression in the macular endothelium compared to peripheral regions, unlike other steroid receptor genes. -expressing endothelial cells display an augmented responsiveness to Transforming growth factor beta (TGF-β), indicating a propensity towards endothelial to mesenchymal transition (endMT) transcriptional profiling.

INTERPRETATION

These results highlight the proclivity of CSCR to manifest primarily within the choroidal vasculature rather than the RPE, suggesting its categorization as a vascular eye disorder. This study accentuates the pivotal role of androgenic steroids, in addition to glucocorticoids. The observed linkage to TGF-β-mediated endMT provides a potential mechanistic insight into the disease's etiology.

摘要

背景

中心性浆液性脉络膜视网膜病变(CSCR)表现为神经感觉视网膜与视网膜色素上皮(RPE)之间的液体积聚。类固醇激素水平升高与 CSCR 的发病机制有关。本研究旨在描绘 CSCR 相关风险和类固醇受体在人脉络膜细胞类型和 RPE 细胞中的基因表达模式,以发现潜在的潜在机制。

方法

本研究利用对非病理人脉络膜和 RPE 细胞的转录组数据的全面查询。

发现

CSCR 相关基因,如 、 等,主要在脉络膜内皮细胞中表达,而不是在 RPE 中表达。雄激素受体由 基因编码,与其他类固醇受体基因不同,在黄斑内皮细胞中的表达高于周边区域。表达 的内皮细胞对转化生长因子-β(TGF-β)表现出增强的反应性,表明其向间充质转化(endMT)转录谱的倾向性。

解释

这些结果突出了 CSCR 主要在脉络膜血管系统而不是 RPE 中表现的倾向,表明其被归类为血管性眼病。本研究强调了雄激素类固醇的关键作用,除了糖皮质激素。观察到与 TGF-β 介导的 endMT 的关联为该疾病的病因提供了潜在的机制见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df15/11408951/31444c23491d/10.1177_11206721241226735-fig1.jpg

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