Autoren:	Prokosch, Verena Brockhaus, Kathrin Anders, Fabian Liu, Hanhan Mercieca, Karl Gericke, Adrian Melkonyan, Harut Thanos, Solon
Titel:	Elevated intraocular pressure induces neuron-specific β-III-tubulin expression in non-neuronal vascular cells
Online-Publikationsdatum:	8-Jun-2022
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	PURPOSE 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.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7094
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY-NC
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by-nc/4.0/
Zeitschrift:	Acta ophthalmologica 98 5
Seitenzahl oder Artikelnummer:	e617 e630
Verlag:	Blackwell
Verlagsort:	Oxford
Erscheinungsdatum:	2020
ISSN:	1755-3768
DOI der Originalveröffentlichung:	10.1111/aos.14333
Enthalten in den Sammlungen:	JGU-Publikationen