通过缺氧成像预测视网膜分支动脉闭塞的原发性神经元细胞损伤

IF 1.9 4区 医学 Q3 HEMATOLOGY
Sara Z. Jamal, Blake W. Dieckmann, Gary W. McCollum, John S. Penn, Ashwath Jayagopal, MD Imam Uddin
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引用次数: 0

摘要

目的:利用激光诱导的小鼠视网膜大动脉血栓形成,建立视网膜分支动脉闭塞(BRAO)小鼠模型的可靠方法。同时,开发一种检测视网膜缺氧的可靠方法,作为 BRAO 中神经细胞损伤风险的预测性生物标志物:方法:在小鼠视网膜上用玫瑰红染色法建立了一个可靠、可重复的激光诱导 BRAO 模型。为了描述 BRAO 中视网膜缺氧的特征,采用了波尼哒唑免疫染色法和 HYPOX-4 分子成像法。末端脱氧核苷酸转移酶 dUTP 缺口标记(TUNEL)用于描述 BRAO 视网膜神经细胞损伤的特征。使用 qRT-PCR 分析了 BRAO 视网膜组织和年龄匹配的对照视网膜组织中 mRNA 的表达:结果:视神经头(ONH)附近的视网膜分支动脉闭塞导致视网膜组织缺氧,缺氧面积约占整个视网膜的 12.5%。在 BRAO 视网膜组织横切面上,TUNEL 阳性细胞分布在所有视网膜层。此外,qRT-PCR 数据分析表明,BRAO 与炎症和缺氧有关:本研究提供了一种可靠的小鼠视网膜 BRAO 检测方法,并证明了分子成像方法在检测视网膜缺氧方面的实用性,可作为 BRAO 神经元细胞损伤风险的预测性生物标志物。此外,我们的数据还表明,BRAO 视网膜与炎症有关,也与缺氧相关的神经细胞损伤有关:视网膜缺氧区域成像可提供准确诊断,评估 BRAO 引起的视网膜组织损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion

Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion

Purpose

To develop a reliable method to generate a mouse model of branch retinal artery occlusion (BRAO) using laser-induced thrombosis of a major artery in the mouse retina. Also, to develop a reliable method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO.

Methods

A reliable and reproducible model of laser-induced BRAO was developed in mouse retina using Rose Bengal. To characterize retinal hypoxia in BRAO, pimonidazole immunostaining and HYPOX-4 molecular imaging methods were used. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used to characterize neuronal cell damage in the BRAO retina. Expression of mRNA in retinal tissues from BRAO and age-matched control retinas were analyzed using qRT-PCR.

Results

Occlusion of a branch retinal artery near the optic nerve head (ONH) caused a pattern of retinal tissue hypoxia covering about 12.5% of the entire retina. TUNEL-positive cells were localized in all layers in BRAO retinal tissue cross sections. In addition, qRT-PCR data analysis suggests that BRAO is associated with both inflammation and hypoxia.

Conclusions

This study provides a reliable method for BRAO in mouse retina and demonstrates the utility of molecular imaging method to detect retinal hypoxia as predictive biomarker for the risk of neuronal cell damage in BRAO. In addition, our data suggest that BRAO retinas are associated with inflammation and also associated with hypoxia-related neuronal cell damage.

Perspectives

Imaging areas of retinal hypoxia may provide accurate diagnosis, evaluating retinal tissue injury from BRAO.

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来源期刊
Microcirculation
Microcirculation 医学-外周血管病
CiteScore
5.00
自引率
4.20%
发文量
43
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.
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