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@ARTICLE{Bell:151653,
author = {Bell, Katharina and Rosignol, Ines and Sierra-Filardi,
Elena and Rodriguez-Muela, Natalia and Schmelter, Carsten
and Cecconi, Francesco and Grus, Franz and Boya, Patricia},
title = {{A}ge related retinal {G}anglion cell susceptibility in
context of autophagy deficiency},
journal = {Cell death discovery},
volume = {6},
number = {1},
issn = {2058-7716},
address = {London},
publisher = {Nature Publishing Group306324},
reportid = {DZNE-2020-01232},
pages = {21},
year = {2020},
abstract = {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.},
cin = {AG Rodriguez-Muela},
ddc = {610},
cid = {I:(DE-2719)1713001},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32337073},
pmc = {pmc:PMC7165178},
doi = {10.1038/s41420-020-0257-4},
url = {https://pub.dzne.de/record/151653},
}