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Elevated Intraocular Pressure Causes Abnormal Reactivity of Mouse Retinal Arterioles.

Abstract：

Objective:Glaucoma is a leading cause of severe visual impairment and blindness. Although high intraocular pressure (IOP) is an established risk factor for the disease, the role of abnormal ocular vessel function in the pathophysiology of glaucoma gains more and more attention. We tested the hypothesis that elevated intraocular pressure (IOP) causes vascular dysfunction in the retina. Methods:High IOP was induced in one group of mice by unilateral cauterization of three episcleral veins. The other group received sham surgery only. Two weeks later, retinal vascular preparations were studied by video microscopy in vitro. Reactive oxygen species (ROS) levels and expression of hypoxia markers and of prooxidant and antioxidant redox genes as well as of inflammatory cytokines were determined. Results:Strikingly, responses of retinal arterioles to stepwise elevation of perfusion pressure were impaired in the high-IOP group. Moreover, vasodilation responses to the endothelium-dependent vasodilator, acetylcholine, were markedly reduced in mice with elevated IOP, while no differences were seen in response to the endothelium-independent nitric oxide donor, sodium nitroprusside. Remarkably, ROS levels were increased in the retinal ganglion cell layer including blood vessels. Expression of the NADPH oxidase isoform, NOX2, and of the inflammatory cytokine, TNF-α, was increased at the mRNA level in retinal explants. Expression of NOX2, but not of the hypoxic markers, HIF-1α and VEGF-A, was increased in the retinal ganglion cell layer and in retinal blood vessels at the protein level. Conclusion:Our data provide first-time evidence that IOP elevation impairs autoregulation and induces endothelial dysfunction in mouse retinal arterioles. Oxidative stress and inflammation, but not hypoxia, appear to be involved in this process.

journal_name

Oxid Med Cell Longev

journal_title

Oxidative medicine and cellular longevity

authors

Gericke A,Mann C,Zadeh JK,Musayeva A,Wolff I,Wang M,Pfeiffer N,Daiber A,Li H,Xia N,Prokosch V

doi

10.1155/2019/9736047

subject

Has Abstract

pub_date

2019-12-29 00:00:00

pages

9736047

eissn

1942-0900

issn

1942-0994

journal_volume

2019

pub_type

杂志文章

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Elevated Intraocular Pressure Causes Abnormal Reactivity of Mouse Retinal Arterioles.