151653 20240423115948.0 pmid:32337073 pmid 10.1038/s41420-020-0257-4 doi altmetric:80028848 altmetric pmc:PMC7165178 pmc DZNE-2020-01232 610 Bell, Katharina P:(DE-HGF)0 0 Corresponding author Age related retinal Ganglion cell susceptibility in context of autophagy deficiency London 2020 Nature Publishing Group306324 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1713781020_6651 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Glaucoma 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. 344 - Clinical and Health Care Research (POF3-344) G:(DE-HGF)POF3-344 POF3-344 POF III 0 Dataset connected to CrossRef Rosignol, Ines P:(DE-HGF)0 1 Sierra-Filardi, Elena 2 Rodriguez-Muela, Natalia P:(DE-2719)9000726 3 dzne Schmelter, Carsten 4 Cecconi, Francesco 5 Grus, Franz 6 Boya, Patricia 0000-0003-3045-951X 7 Corresponding author 10.1038/s41420-020-0257-4 Vol. 6, no. 1, p. 21 PERI:(DE-600)2842546-7 1 21 Cell death discovery 6 2020 2058-7716 https://www.nature.com/articles/s41420-020-0257-4 http://pub.dzne.de/record/151653/files/DZNE-2020-01232.pdf OpenAccess http://pub.dzne.de/record/151653/files/DZNE-2020-01232.pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:151653 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)9000726 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-344 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2020 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-03-31 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2020-01-11 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-03-31 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2020-01-11 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-03-31 JCR StatID:(DE-HGF)0100 StatID CELL DEATH DISCOV : 2021 2023-03-31 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-02-14T16:19:13Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-02-14T16:19:13Z DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-03-31 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-03-31 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-03-31 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-02-14T16:19:13Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2020-01-11 IF >= 5 StatID:(DE-HGF)9905 StatID CELL DEATH DISCOV : 2021 2023-03-31 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2020-01-11 Fees StatID:(DE-HGF)0700 StatID 2020-01-11 I:(DE-2719)1713001 AG Rodriguez-Muela Selective Neuronal Vulnerability in Neurodegenerative Diseases 0 journal VDB UNRESTRICTED I:(DE-2719)1713001 FullTexts