Autoren:	Lauzi, Jasmin Anders, Fabian Liu, Hanhan Pfeiffer, Norbert Grus, Franz-Hermann Thanos, Solon Arnhold, Stefan Prokosch-Willing, Verena
Titel:	Neuroprotective and neuroregenerative effects of CRMP-5 on retinal ganglion cells in an experimental in vivo and in vitro model of glaucoma
Online-Publikationsdatum:	11-Jul-2019
Erscheinungsdatum:	2019
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Purpose To analyze the potential neuro-protective and neuro-regenerative effects of Collapsin-response response-mediator-protein-5 (CRMP-5) on retinal ganglion cells (RGCs) using in vitro and in vivo animal animal models of glaucoma. Methods Elevated intraocular pressure (IOP) was induced in adult female female Sprague-Dawley (SD) rats by cauterization of three episcleral veins. Changes in CRMP-5 expression expression within the retinal proteome were analyzed via label-free mass spectrometry. In vitro, retinal explants were cultured under elevated pressure (60 mmHg) within a high-pressure incubation chamber chamber with and without addition of different concentrations of CRMP-5 (4 μg/l, 200 μg/l and 400 μ μg/l). In addition, retinal explants were cultured under regenerative conditions with and without application of 200 μg/l CRMP-5 after performing an optic nerve crush (ONC). Thirdly, an antibody against Protein Kinase B (PKB) was added to examine the possible effects of CRMP-5. RGC count was performed. Number and length of the axons were determined and compared. To undermine a signal-transduction transduction pathway via CRMP-5 and PKB microarray and immunohistochemistry were performed. Results CRMP-5 was downregulated threefold in animals showing chronically elevated IOP. The addition addition of CRMP-5 to retinal culture significantly increased RGC numbers under pressure in a dose-dependent dependent manner and increased and elongated outgrowing axons in retinal explants significantly which which could be blocked by PKB. Especially the number of neurites longer than 400 μm significantly increased increased after application of CRMP-5. CRMP-5 as well as PKB were detected higher in the experimental than in the control group. Conclusion CRMP-5 seems to play an important role in an animal animal model of glaucoma. Addition of CRMP-5 exerts neuro-protective and neuro-regenerative effects in vitro. This effect could be mediated via activation of PKB affecting intra-cellular apoptosis pathways pathways.
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-177
URN:	urn:nbn:de:hebis:77-publ-591463
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	PLOS ONE 14 1
Seitenzahl oder Artikelnummer:	e0207190
Verlag:	PLOS
Verlagsort:	San Francisco, California, US
Erscheinungsdatum:	2019
ISSN:	1932-6203
URL der Originalveröffentlichung:	http://dx.doi.org/10.1371/journal.pone.0207190
DOI der Originalveröffentlichung:	10.1371/journal.pone.0207190
Anmerkung:	Prokosch-Willing, Verena veröffentlicht unter: Prokosch, Verena
Enthalten in den Sammlungen:	JGU-Publikationen