中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (3): 512-518.doi: 10.4103/1673-5374.266069

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

适用于高血压性视网膜神经病变研究的BPH/2J遗传性高血压小鼠模型

  

  • 出版日期:2020-03-15 发布日期:2020-05-26
  • 基金资助:

    该研究由皇家珀斯医院医学研究基金会资助

The Schlager mouse as a model of altered retinal phenotype

Lakshini Y. Herat1, Aaron L. Magno2, Márcio G. Kiuchi3, Kristy L. Jackson4, Revathy Carnagarin3, Geoffrey A. Head4, Markus P. Schlaich3, 5, Vance B. Matthews1   

  1. 1 Dobney Hypertension Centre, School of Biomedical Science - Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
    2 Research Centre, Royal Perth Hospital, Perth, Australia
    3 Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
    4 Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
    5 Department of Cardiology and Department of Nephrology, Royal Perth Hospital, Perth, Australia
  • Online:2020-03-15 Published:2020-05-26
  • Contact: Vance B. Matthews, PhD,vance.matthews@uwa.edu.au.
  • Supported by:
    The study was generously funded by grants from the Royal Perth Hospital Medical Research Foundation (to VBM and MPS).

摘要:

高血压是视力损伤性眼病的主要危险因素。BPH / 2J小鼠选择性近交小鼠品系,由于其交感神经系统活性升高而发展成慢性高血压。实验首次研究了高血压BPH / 2J小鼠(Schlager小鼠)的视网膜神经结构,并将其与正常血压BPN / 3J小鼠进行比较。与正常血压BPN / 3J小鼠相比,高血压BPH / 2J小鼠在21周龄时视网膜神经上皮完全丧失。为了阐明BPH / 2J小鼠视网膜神经结构变化是否归因于高血压,实验比较了4周龄时正常血压BPN / 3J和高血压BPH / 2J小鼠的视网膜神经上皮。结果表明高血压BPH / 2J小鼠在4周龄时发展为严重的视网膜神经损伤,从而表明,高血压BPH / 2J小鼠的视网膜神经损伤与血压升高有关。进一步表征高血压BPH / 2J小鼠品系可能有如下收获:(1)阐明视网膜疾病的基因缺陷; (2)了解导致神经视网膜疾病的机制;(3)允许测试分子用于转化研究以干扰视网膜疾病的进展。

orcid: 0000-0001-9804-9344 (Vance B. Matthews)

关键词:

血压, 眼睛, 高血压, 老鼠, 神经再生, 视网膜, 施拉格鼠, 交感神经系统

Abstract: Hypertension is a risk factor for a large number of vision-threatening eye disorders. In this study, we investigated for the first time the retinal neural structure of the hypertensive BPH/2J mouse (Schlager mouse) and compared it to its control counterpart, the normotensive BPN/3J strain. The BPH/2J mouse is a selectively inbred mouse strain that develops chronic hypertension due to elevated sympathetic nervous system activity. When compared to the BPN/3J strain, the hypertensive BPH/2J mice showed a complete loss of outer layers of the neural retina at 21 weeks of age, which was indicative of a severe vision-threatening disease potentially caused by hypertension. To elucidate whether the retinal neural phenotype in the BPH/2J strain was attributed to increased BP, we investigated the neural retina of both BPN/3J and BPH/2J mice at 4 weeks of age. Our preliminary results showed for the first time that the BPH/2J strain develops severe retinal neural damage at a young age. Our findings suggest that the retinal phenotype in the BPH/2J mouse is possibly due to elevated blood pressure and may be contributed by an early onset spontaneous mutation which is yet to be identified or a congenital defect occurring in this strain. Further characterization of the BPH/2J mouse strain is likely to i) elucidate gene defects underlying retinal disease; ii) understand mechanisms leading to neural retinal disease and iii) permit testing of molecules for translational research to interfere with the progression of retinal disease. The animal experiments were performed with the approval of the Royal Perth Hospital Animal Ethics Committee (R535/17-18) on June 1, 2017.

Key words: blood pressure, eye, hypertension, mice, neural regeneration, retina, Schlager mouse, sympathetic nervous system