Retinoid signaling regulates angiogenesis and blood-retinal barrier integrity in neonatal mouse retina

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2022-02-24 DOI:10.1111/micc.12752

Eric Engelbrecht, Melissa A. Metzler, Lisa L. Sandell

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引用次数: 3

Abstract

Objective

The neonatal mouse retina is a well-characterized experimental model for investigating factors impacting retinal angiogenesis and inner blood-retinal barrier (BRB) integrity. Retinoic acid (RA) is an essential signaling molecule. RA is needed for vasculogenic development in embryos and endothelial barrier integrity in zebrafish retina and adult mouse brain; however, the function of this signaling molecule in developing mammalian retinal vasculature remains unknown. This study aims to investigate the role of RA signaling in angiogenesis and inner BRB integrity in mouse neonatal retina.

Methods

RA distribution in the developing neurovascular retina was assessed in mice carrying an RA-responsive transgene. RA function in retinal angiogenesis was determined by treating C57BL/6 neonatal pups with a pharmacological inhibitor of RA signaling BMS493 or control vehicle. BRB integrity assessed by monitoring leakage of injected tracer into extravascular retinal tissue.

Results

RA signaling activity is present in peripheral astrocytes in domains corresponding to RA activity of the underlying neural retina. RA inhibition impaired retinal angiogenesis and reduced endothelial cell proliferation. RA inhibition also compromised BRB integrity. Vascular leakage was not associated with altered expression of CLDN5, PLVAP, LEF1, or VEcad.

Conclusions

RA signaling is needed for angiogenesis and integrity of the BRB in the neonatal mouse retina.

Abstract Image

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类视黄醇信号调节新生小鼠视网膜血管生成和血视网膜屏障完整性

目的新生小鼠视网膜是研究影响视网膜血管生成和血液-视网膜屏障(BRB)完整性因素的实验模型。视黄酸(RA)是一种重要的信号分子。类风湿关节炎是胚胎血管形成发育和斑马鱼视网膜和成年小鼠脑内皮屏障完整性所必需的;然而，该信号分子在哺乳动物视网膜血管发育中的作用尚不清楚。本研究旨在探讨RA信号在小鼠新生视网膜血管生成和内部BRB完整性中的作用。方法采用RA应答转基因小鼠，观察RA在发育中的神经血管视网膜中的分布。通过RA信号BMS493药理抑制剂或对照物治疗C57BL/6新生幼崽，观察RA在视网膜血管生成中的功能。通过监测注射示踪剂渗漏到血管外视网膜组织来评估BRB的完整性。结果外周星形胶质细胞的RA信号活动与视网膜下神经的RA活动相对应。RA抑制抑制视网膜血管生成，减少内皮细胞增殖。RA抑制也损害了BRB的完整性。血管渗漏与CLDN5、PLVAP、LEF1或VEcad的表达改变无关。结论RA信号是新生小鼠视网膜血管生成和BRB完整性所必需的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.