Original research: Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma

BMJ Open Ophthalmology

article

Stephan Alexander Fraenkl¹  Quentin Simon²  Yeni Yucel³  Neeru Gupta³  Valéry V Wittwer¹  Beatrice E Frueh¹  Stefan A Tschanz² 

[1] Department of Ophthalmology, Inselspital , University of Bern;Institute of Anatomy , University of Bern;Keenan Research Centre , St Michael's Hospital Li Ka Shing Knowledge Institute;Department of Ophthalmology and Vision Sciences , University of Toronto;Ophthalmologic Network Organization

关键词: Glaucoma;    Anatomy;    Experimental & animal models;    Optic Nerve;   

DOI  :  10.1136/bmjophth-2022-001078

学科分类：工业工程学

来源: BMJ Publishing Group

【 摘 要 】

Objective One of the most important risk factors for developing a glaucomatous optic neuropathy is elevated intraocular pressure. Moreover, mechanisms such as altered perfusion have been postulated to injure the optical path. In a mouse model, we compare first negative effects of cerebral perfusion/reperfusion on the optic nerve structure versus alterations by elevated intraocular pressure. Second, we compare the alterations by isolated hypoperfusion-reperfusion and isolated intraocular pressure to the combination of both.Methods and analysis Mice were divided in four groups: (1) controls; (2) perfusion altered mice that underwent transient bi-common carotid artery occlusion (BCCAO) for 40 min; (3) glaucoma group (DBA/2J mice); (4) combined glaucoma and altered perfusion (DBA/2J mice with transient BCCAO). Optic nerve sections were stereologically examined 10–12 weeks after intervention.Results All experimental groups showed a decreased total axon number per optic nerve compared with controls. In DBA/2J and combined DBA/2J & BCCAO mice the significant decrease was roughly 50%, while BCCAO leaded to a 23% reduction of axon number, however reaching significance only in the direct t-test. The difference in axon number between BCCAO and both DBA/2J mice was almost 30%, lacking statistical significance due to a remarkably high variation in both DBA/2J groups.Conclusion Elevated intraocular pressure in the DBA/2J mouse model of glaucoma leads to a much more pronounced optic nerve atrophy compared with transient forebrain hypoperfusion and reperfusion by BCCAO. A supposed worsening effect of an altered perfusion added to the pressure-related damage could not be detected.

【 授权许可】

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