000151653 001__ 151653
000151653 005__ 20240423115948.0
000151653 0247_ $$2pmid$$apmid:32337073
000151653 0247_ $$2doi$$a10.1038/s41420-020-0257-4
000151653 0247_ $$2altmetric$$aaltmetric:80028848
000151653 0247_ $$2pmc$$apmc:PMC7165178
000151653 037__ $$aDZNE-2020-01232
000151653 082__ $$a610
000151653 1001_ $$0P:(DE-HGF)0$$aBell, Katharina$$b0$$eCorresponding author
000151653 245__ $$aAge related retinal Ganglion cell susceptibility in context of autophagy deficiency
000151653 260__ $$aLondon$$bNature Publishing Group306324$$c2020
000151653 3367_ $$2DRIVER$$aarticle
000151653 3367_ $$2DataCite$$aOutput Types/Journal article
000151653 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1713781020_6651
000151653 3367_ $$2BibTeX$$aARTICLE
000151653 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000151653 3367_ $$00$$2EndNote$$aJournal Article
000151653 520__ $$aGlaucoma is a common age-related disease leading to progressive retinal ganglion cell (RGC) death, visual field defects and vision loss and is the second leading cause of blindness in the elderly worldwide. Mitochondrial dysfunction and impaired autophagy have been linked to glaucoma and induction of autophagy shows neuroprotective effects in glaucoma animal models. We have shown that autophagy decreases with aging in the retina and that autophagy can be neuroprotective for RGCs, but it is currently unknown how aging and autophagy deficiency impact RGCs susceptibility and survival. Using the optic nerve crush model in young and olWelcome@1234d Ambra1+/gt (autophagy/beclin-1 regulator 1+/gt) mice we analysed the contribution of autophagy deficiency on retinal ganglion cell survival in an age dependent context. Interestingly, old Ambra1+/gt mice showed decreased RGC survival after optic nerve crush in comparison to old Ambra1+/+, an effect that was not observed in the young animals. Proteomics and mRNA expression data point towards altered oxidative stress response and mitochondrial alterations in old Ambra1+/gt animals. This effect is intensified after RGC axonal damage, resulting in reduced oxidative stress response showing decreased levels of Nqo1, as well as failure of Nrf2 induction in the old Ambra1+/gt. Old Ambra1+/gt also failed to show increase in Bnip3l and Bnip3 expression after optic nerve crush, a response that is found in the Ambra1+/+ controls. Primary RGCs derived from Ambra1+/gt mice show decreased neurite projection and increased levels of apoptosis in comparison to Ambra1+/+ animals. Our results lead to the conclusion that oxidative stress response pathways are altered in old Ambra1+/gt mice leading to impaired damage responses upon additional external stress factors.
000151653 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000151653 588__ $$aDataset connected to CrossRef
000151653 7001_ $$0P:(DE-HGF)0$$aRosignol, Ines$$b1
000151653 7001_ $$aSierra-Filardi, Elena$$b2
000151653 7001_ $$0P:(DE-2719)9000726$$aRodriguez-Muela, Natalia$$b3$$udzne
000151653 7001_ $$aSchmelter, Carsten$$b4
000151653 7001_ $$aCecconi, Francesco$$b5
000151653 7001_ $$aGrus, Franz$$b6
000151653 7001_ $$00000-0003-3045-951X$$aBoya, Patricia$$b7$$eCorresponding author
000151653 773__ $$0PERI:(DE-600)2842546-7$$a10.1038/s41420-020-0257-4$$gVol. 6, no. 1, p. 21$$n1$$p21$$tCell death discovery$$v6$$x2058-7716$$y2020
000151653 8564_ $$uhttps://www.nature.com/articles/s41420-020-0257-4
000151653 8564_ $$uhttps://pub.dzne.de/record/151653/files/DZNE-2020-01232.pdf$$yOpenAccess
000151653 8564_ $$uhttps://pub.dzne.de/record/151653/files/DZNE-2020-01232.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000151653 909CO $$ooai:pub.dzne.de:151653$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
000151653 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000726$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000151653 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000151653 9141_ $$y2020
000151653 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-03-31
000151653 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2020-01-11
000151653 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2020-01-11
000151653 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCELL DEATH DISCOV : 2021$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-02-14T16:19:13Z
000151653 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-02-14T16:19:13Z
000151653 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000151653 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2021-02-14T16:19:13Z
000151653 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$f2020-01-11
000151653 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCELL DEATH DISCOV : 2021$$d2023-03-31
000151653 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-01-11
000151653 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2020-01-11
000151653 9201_ $$0I:(DE-2719)1713001$$kAG Rodriguez-Muela$$lSelective Neuronal Vulnerability in Neurodegenerative Diseases$$x0
000151653 980__ $$ajournal
000151653 980__ $$aVDB
000151653 980__ $$aUNRESTRICTED
000151653 980__ $$aI:(DE-2719)1713001
000151653 9801_ $$aFullTexts