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dc.contributor.authorChrysostomou, V
dc.contributor.authorGalic, S
dc.contributor.authorvan Wijngaarden, P
dc.contributor.authorTrounce, IA
dc.contributor.authorSteinberg, GR
dc.contributor.authorCrowston, JG
dc.date.accessioned2021-02-05T01:01:33Z
dc.date.available2021-02-05T01:01:33Z
dc.date.issued2016-12-01
dc.identifier.citationChrysostomou, V., Galic, S., van Wijngaarden, P., Trounce, I. A., Steinberg, G. R. & Crowston, J. G. (2016). Exercise reverses age-related vulnerability of the retina to injury by preventing complement-mediated synapse elimination via a BDNF-dependent pathway. AGING CELL, 15 (6), pp.1082-1091. https://doi.org/10.1111/acel.12512.
dc.identifier.issn1474-9718
dc.identifier.urihttp://hdl.handle.net/11343/260244
dc.description.abstractRetinal ganglion cells (RGCs) become increasingly vulnerable to injury with advancing age. We recently showed that this vulnerability can be strongly modified in mice by exercise. However, the characteristics and underlying mechanisms of retinal protection with exercise remain unknown. Hence, the aim of this study was to investigate cellular changes associated with exercise-induced protection of aging retinal cells and the role of local and peripheral trophic signalling in mediating these effects. We focussed on two molecules that are thought to play key roles in mediating beneficial effects of exercise: brain-derived neurotrophic factor (BDNF) and AMP-activated protein kinase (AMPK). In middle-aged (12 months old) C57BL/6J mice, we found that exercise protected RGCs against dysfunction and cell loss after an acute injury induced by elevation of intra-ocular pressure. This was associated with preservation of inner retinal synapses and reduced synaptic complement deposition. Retinal expression of BDNF was not upregulated in response to exercise alone. Rather, exercise maintained BDNF levels in the retina, which were decreased postinjury in nonexercised animals. Confirming a critical role for BDNF, we found that blocking BDNF signalling during exercise by pharmacological means or genetic knock-down suppressed the functional protection of RGCs afforded by exercise. Protection of RGCs with exercise was independent of activation of AMPK in either retina or skeletal muscle. Our data support a previously unidentified mechanism in which exercise prevents loss of BDNF in the retina after injury and preserves neuronal function and survival by preventing complement-mediated elimination of synapses.
dc.languageEnglish
dc.publisherWILEY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleExercise reverses age-related vulnerability of the retina to injury by preventing complement-mediated synapse elimination via a BDNF-dependent pathway
dc.typeJournal Article
dc.identifier.doi10.1111/acel.12512
melbourne.affiliation.departmentMedicine (St Vincent's)
melbourne.affiliation.departmentOphthalmology (Eye & Ear Hospital)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleAging Cell
melbourne.source.volume15
melbourne.source.issue6
melbourne.source.pages1082-1091
dc.rights.licenseCC BY
melbourne.elementsid1097735
melbourne.contributor.authorvan Wijngaarden, Peter
melbourne.contributor.authorCrowston, Jonathan
melbourne.contributor.authorTrounce, Ian
melbourne.contributor.authorGalic, Sandra
dc.identifier.eissn1474-9726
melbourne.accessrightsOpen Access


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