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

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...

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Autores principales: Fraenkl, Stephan Alexander, Simon, Quentin, Yucel, Yeni, Gupta, Neeru, Wittwer, Valéry V, Frueh, Beatrice E, Tschanz, Stefan A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476133/
https://www.ncbi.nlm.nih.gov/pubmed/36161839
http://dx.doi.org/10.1136/bmjophth-2022-001078
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author Fraenkl, Stephan Alexander
Simon, Quentin
Yucel, Yeni
Gupta, Neeru
Wittwer, Valéry V
Frueh, Beatrice E
Tschanz, Stefan A
author_facet Fraenkl, Stephan Alexander
Simon, Quentin
Yucel, Yeni
Gupta, Neeru
Wittwer, Valéry V
Frueh, Beatrice E
Tschanz, Stefan A
author_sort Fraenkl, Stephan Alexander
collection PubMed
description 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.
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spelling pubmed-94761332022-09-16 Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma Fraenkl, Stephan Alexander Simon, Quentin Yucel, Yeni Gupta, Neeru Wittwer, Valéry V Frueh, Beatrice E Tschanz, Stefan A BMJ Open Ophthalmol Glaucoma 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. BMJ Publishing Group 2022-09-14 /pmc/articles/PMC9476133/ /pubmed/36161839 http://dx.doi.org/10.1136/bmjophth-2022-001078 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Glaucoma
Fraenkl, Stephan Alexander
Simon, Quentin
Yucel, Yeni
Gupta, Neeru
Wittwer, Valéry V
Frueh, Beatrice E
Tschanz, Stefan A
Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma
title Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma
title_full Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma
title_fullStr Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma
title_full_unstemmed Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma
title_short Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma
title_sort impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the dba/2j mouse model of glaucoma
topic Glaucoma
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476133/
https://www.ncbi.nlm.nih.gov/pubmed/36161839
http://dx.doi.org/10.1136/bmjophth-2022-001078
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