Elevated intraocular pressure induces neuron-specific β-III-tubulin expression in non-neuronal vascular cells

dc.contributor.authorProkosch, Verena
dc.contributor.authorBrockhaus, Kathrin
dc.contributor.authorAnders, Fabian
dc.contributor.authorLiu, Hanhan
dc.contributor.authorMercieca, Karl
dc.contributor.authorGericke, Adrian
dc.contributor.authorMelkonyan, Harut
dc.contributor.authorThanos, Solon
dc.date.accessioned2022-06-08T09:35:43Z
dc.date.available2022-06-08T09:35:43Z
dc.date.issued2020
dc.description.abstractPURPOSE Pathological alterations within optic nerve axons and progressive loss of the parental retinal ganglion cell (RGC) bodies are characteristics of glaucomatous neuropathy. Abnormally elevated intraocular pressure (IOP) is thought to be the major risk factor for most forms of glaucomatous changes, while lowering of the IOP is the mainstream of treatment. However, the pathophysiological mechanisms involved in neurodegenerative changes are poorly understood. It remains still a matter of debate whether elevated IOP harms the neurons directly or indirectly through alterations in the retinal vascularization. METHODS We analysed morphological and molecular changes within the retina exposed to elevated IOP in an animal model of glaucoma in vivo, in retinal explants and in cultured dissociated retinal cells each incubated under elevated air pressure in vitro, imitating elevated IOP. RESULTS Although ß-III-tubulin expressing RGCs decreased within the course of the disease, total amount of ß-III-tubulin protein within the retina increased, leading to the assumption that other cells than RGCs abnormally express ß-III-tubulin due to elevated IOP. Surprisingly, we found that β-III-tubulin, a marker developmentally regulated and specifically expressed in neurons under normal conditions, was strongly up-regulated in desmin-, PDGFR-β- and α-SMA-positive pericytes as well as in endothelin-1-positive endothelial cells both in vivo under elevated IOP and in vitro under elevated culture atmosphere pressure that simulated IOP elevation. Beta-III-tubulin-driven signalling pathways (ERK 1/2, pERK1/2 and cdc42/Rac) were also regulated. CONCLUSION The unprecedented regulation of neuron-specific β-III-tubulin in pericytes and endothelial cells is likely associated with a role of the retinal vasculature in the IOP-induced development and manifestation of glaucomatous degenerative optic nerve response.en_GB
dc.identifier.doihttp://doi.org/10.25358/openscience-7094
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7108
dc.language.isoengde
dc.rightsCC-BY-NC-4.0*
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleElevated intraocular pressure induces neuron-specific β-III-tubulin expression in non-neuronal vascular cellsen_GB
dc.typeZeitschriftenaufsatzde
jgu.journal.issue5de
jgu.journal.titleActa ophthalmologicade
jgu.journal.volume98de
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number2700
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.ende630de
jgu.pages.starte617de
jgu.publisher.doi10.1111/aos.14333de
jgu.publisher.issn1755-3768de
jgu.publisher.nameBlackwellde
jgu.publisher.placeOxfordde
jgu.publisher.year2020
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode610de
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
elevated_intraocular_pressure-20220608113010362.pdf
Size:
9.22 MB
Format:
Adobe Portable Document Format
Description:

License bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
3.57 KB
Format:
Item-specific license agreed upon to submission
Description: