The pathological association between the anterior eye segment and the retina in a murine model of neovascular glaucoma

The pathological association between the anterior eye segment and the retina in a murine model of neovascular glaucoma
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新生血管性青光眼小鼠模型眼前段与视网膜的病理关联

DOI:
10.1096/fj.202101917r
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发表时间:
2022
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
Hara Hideaki
Hara Hideaki
中科院分区:
--
文献类型:
--
作者:
Nishinaka Anri;Tanaka Miruto;Aoshima Kota;Kuriyama Aika;Sasaki Takahiro;Otsu Wataru;Yasuda Hiroto;Nakamura Shinsuke;Shimazawa Masamitsu;Hara Hideaki

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新生血管性青光眼(NVG)是由视网膜缺血性疾病(如增殖性糖尿病视网膜病变(PDR)和视网膜静脉阻塞(RVO))中的房角、虹膜和角膜中新血管的形成引起的,其可降低视力。然而,NVG的病理生理学症状仍然没有得到很好的理解,因为没有NVG在角、虹膜和角膜中形成的模型。本研究的目的是在视网膜缺血的小鼠模型中调查缺血性疾病期间NVG的参与。我们评估了该模型中眼内压(IOP)和眼前段和视网膜的病理症状的变化,并通过定量真实的时间聚合酶链反应或蛋白质印迹法分别分析了视网膜和角膜中血管内皮生长因子(VEGF)和纤维化相关因子的RNA或蛋白表达的变化。此外,我们检查了玻璃体内注射抗VEGF抗体后IOP的变化。首先,在视网膜缺血小鼠模型中形成NVG,并且形成NVG的小鼠的IOP升高。有趣的是,在NVG小鼠模型中,视网膜中VEGF表达减少,但角膜中VEGF表达增加。另一方面,NVG中视网膜中的纤维化相关因子增加,角膜中的纤维化相关因子也显著增加。此外,血管闭塞后立即给予抗VEGF抗体抑制了IOP的升高,但血管闭塞后7天给予抗VEGF抗体加速了IOP的升高。提示NVG的形成可能与视网膜缺血性疾病的病理症状、VEGF及纤维化相关因子表达的改变有关。
Neovascular glaucoma (NVG) is caused by the formation of new blood vessels in the angle, iris, and cornea in retinal ischemic disease, such as proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO), which can reduce the visual acuity. However, the pathophysiological symptoms of NVG are still not well understood because there is no model for the formation of NVG in the angle, iris, and cornea. The aim of this study was to investigate the involvement of NVG during ischemic disease, in a murine model of retinal ischemia. We evaluated the changes of the intraocular pressure (IOP) and pathological symptoms in the anterior eye segment and retina in this model, and the changes in the RNA or protein expression of vascular endothelial growth factor (VEGF) and fibrosis‐related factors were analyzed in the retina and cornea by quantitative real‐time polymerase chain reaction or western blot, respectively. Furthermore, we examined the changes in IOP after intravitreal injection of an anti‐VEGF antibody. First, NVG formed in the retinal ischemic murine model, and the IOP was elevated in mice with NVG formation. Interestingly, VEGF expression was decreased in the retina but increased in the cornea in the murine model of NVG. On the other hand, fibrosis‐related factors were increased in the retina and also significantly increased in the cornea in NVG. Moreover, the administration of anti‐VEGF antibody immediately after vessel occlusion suppressed the increase in IOP, but administration at 7 days after vessel occlusion accelerated the increase in IOP. These findings suggest that the formation of NVG may be correlated with the pathological symptoms of retinal ischemic disease,viachanges in VEGF and fibrosis‐related factor expression.
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