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MANF delivery improves retinal homeostasis and cell replacement therapies in ageing mice

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dc.contributor.authorNeves, Joana
dc.contributor.authorChirco, Kathleen R.
dc.contributor.authorCedron-Craft, Wendy
dc.contributor.authorChew, Shereen
dc.contributor.authorZhu, Jie
dc.contributor.authorJasper, Heinrich
dc.contributor.authorLamba, Deepak A.
dc.date.accessioned2021-03-26T16:20:02Z
dc.date.available2021-03-26T16:20:02Z
dc.date.issued2020
dc.descriptionCopyright © 2020 Elsevier Inc. All rights reserved.pt_PT
dc.description.abstractAgeing is a major risk factor for vision loss, and inflammation is an important contributor to retinal disease in the elderly. Regenerative medicine based on cell replacement strategies has emerged in recent years as a promising approach to restore vision. However, how the ageing process affects retinal homeostasis and inflammation in the retina and how this may impose a limitation to the success of such interventions remains unknown. Here we report that, in mice and humans, retinal ageing is associated with a reduction in MANF protein levels, specifically in the choroid, where increased densities of activated macrophages can be detected. We further show that the retina of old wild type mice, in the absence of any other genetic alteration, has limited homeostatic capacity after damage imposed by light exposure and reduced engraftment efficiency of exogenously supplied photoreceptors. Finally, we show that supplementation of MANF recombinant protein can improve retinal homeostasis and repair capacity in both settings, correlating with reduced numbers of activated macrophages in the old retina. Our work identifies age-related alterations in retinal homeostasis, independent of genetic alterations, leading to age-related retinal inflammation and damage susceptibility. We suggest that MANF therapy is a potential intervention to maintain retinal homeostasis in the elderly and improve the success of retinal regenerative therapies applied to aged individuals.pt_PT
dc.description.sponsorshipThis work was supported by NIH grants EY025779 to D.A.L. and NIH grants AG052989 and AG047497 to H.J.J.N. was supported by the Glenn Foundation for Medical Researchpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationExp Gerontol. 2020 Feb 28;134:110893pt_PT
dc.identifier.doi10.1016/j.exger.2020.110893pt_PT
dc.identifier.eissn1873-6815
dc.identifier.issn0531-5565
dc.identifier.urihttp://hdl.handle.net/10451/47104
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/experimental-gerontologypt_PT
dc.titleMANF delivery improves retinal homeostasis and cell replacement therapies in ageing micept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage110893pt_PT
oaire.citation.titleExperimental Gerontologypt_PT
oaire.citation.volume134pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT

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