Herat Lakshini Y, Magno Aaron L, Kiuchi Márcio G, Jackson Kristy L, Carnagarin Revathy, Head Geoffrey A, Schlaich Markus P, Matthews Vance B
Dobney Hypertension Centre, School of Biomedical Science - Royal Perth Hospital Unit, University of Western Australia, Perth, Australia.
Research Centre, Royal Perth Hospital, Perth, Australia.
Neural Regen Res. 2020 Mar;15(3):512-518. doi: 10.4103/1673-5374.266069.
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.
高血压是众多威胁视力的眼部疾病的一个风险因素。在本研究中,我们首次对高血压BPH/2J小鼠(施拉格小鼠)的视网膜神经结构进行了研究,并将其与作为对照的正常血压BPN/3J品系进行了比较。BPH/2J小鼠是一种选择性近交小鼠品系,由于交感神经系统活动增强而出现慢性高血压。与BPN/3J品系相比,高血压BPH/2J小鼠在21周龄时视网膜神经外层完全丧失,这表明可能是由高血压导致的一种严重的威胁视力的疾病。为了阐明BPH/2J品系中的视网膜神经表型是否归因于血压升高,我们在4周龄时对BPN/3J和BPH/2J小鼠的神经视网膜进行了研究。我们的初步结果首次表明,BPH/2J品系在幼年时就出现了严重的视网膜神经损伤。我们的研究结果表明,BPH/2J小鼠的视网膜表型可能是由于血压升高,可能是由一个尚未确定的早发性自发突变或该品系中发生的先天性缺陷所致。对BPH/2J小鼠品系的进一步特征描述可能会:i)阐明视网膜疾病潜在的基因缺陷;ii)了解导致神经视网膜疾病的机制;iii)允许对用于转化研究的分子进行测试,以干扰视网膜疾病的进展。动物实验于2017年6月1日在皇家珀斯医院动物伦理委员会(R535/17 - 18)批准下进行。