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视网膜健康与疾病中的盐皮质激素通路。

Mineralocorticoid pathway in retinal health and diseases.

机构信息

Assistance Publique-Hôpitaux de Paris, Hôpital Cochin Ophtalmopole, Paris, France.

Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, Paris, France.

出版信息

Br J Pharmacol. 2022 Jul;179(13):3190-3204. doi: 10.1111/bph.15770. Epub 2022 Jan 28.

Abstract

In the retina, the mineralocorticoid receptor is expressed in retinal and choroidal vessels and in cells from neural and glial origins. Like in the brain, the major ligand of the mineralocorticoid receptor is cortisol, and the mineralocorticoid/glucocorticoid receptor balance regulates the activation of the MR pathway. Experimental mineralocorticoid receptor pathway activation using either pharmacological agents or transgenic manipulation favours retinal and choroidal pathology. In various models of retinal diseases, such as glaucomatous neuropathy, retinopathy of prematurity, ischaemic retinopathies, diabetic retinopathy and choroidal neovascularization, mineralocorticoid receptor antagonism exerts beneficial effects, demonstrating its potential in the treatment of major blinding retinal diseases. But specific formulations are required to optimize the bioavailability of mineralocorticoid receptor antagonists in various compartments of the eye, and molecular biomarkers of mineralocorticoid receptor pathway activation remain to be identified in humans to select patients amenable to clinical trials. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

摘要

在视网膜中,盐皮质激素受体表达于视网膜和脉络膜血管以及神经和神经胶质来源的细胞中。与大脑中一样,盐皮质激素受体的主要配体是皮质醇,盐皮质激素/糖皮质激素受体平衡调节 MR 途径的激活。使用药理学制剂或转基因操作激活实验性盐皮质激素受体途径有利于视网膜和脉络膜的病理改变。在各种视网膜疾病模型中,如青光眼神经病变、早产儿视网膜病变、缺血性视网膜病变、糖尿病性视网膜病变和脉络膜新生血管形成,盐皮质激素受体拮抗作用发挥有益作用,表明其在治疗主要致盲性视网膜疾病方面具有潜力。但是需要特定的制剂来优化眼内各个部位的盐皮质激素受体拮抗剂的生物利用度,并且需要鉴定人类中盐皮质激素受体途径激活的分子生物标志物,以选择适合临床试验的患者。相关文章:本文是醛固酮-盐皮质激素受体信号通路治疗靶向新兴领域专题的一部分。要查看该部分的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

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