CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis
Age-related macular degeneration is characterized by the formation of drusen containing amyloid-β (Aβ) and the degeneration of photoreceptors. To explore the largely unknown role of Aβ in the retina, we investigated the effects on photoreceptors of the oligomeric form of Aβ(1–42). Subretinal injecti...
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Format: | Article |
Language: | English |
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Elsevier
2011-04-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996111000052 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julien Bruban Agathe Maoui Naïma Chalour Na An Laurent Jonet Charles Feumi Jacques Tréton Florian Sennlaub Francine Behar-Cohen Frédéric Mascarelli Virginie Dinet |
spellingShingle |
Julien Bruban Agathe Maoui Naïma Chalour Na An Laurent Jonet Charles Feumi Jacques Tréton Florian Sennlaub Francine Behar-Cohen Frédéric Mascarelli Virginie Dinet CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis Neurobiology of Disease Retina Microglial cells Inflammation Oxidative stress Age-related macular degeneration Alzheimer's disease |
author_facet |
Julien Bruban Agathe Maoui Naïma Chalour Na An Laurent Jonet Charles Feumi Jacques Tréton Florian Sennlaub Francine Behar-Cohen Frédéric Mascarelli Virginie Dinet |
author_sort |
Julien Bruban |
title |
CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis |
title_short |
CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis |
title_full |
CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis |
title_fullStr |
CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis |
title_full_unstemmed |
CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis |
title_sort |
ccr2/ccl2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2011-04-01 |
description |
Age-related macular degeneration is characterized by the formation of drusen containing amyloid-β (Aβ) and the degeneration of photoreceptors. To explore the largely unknown role of Aβ in the retina, we investigated the effects on photoreceptors of the oligomeric form of Aβ(1–42). Subretinal injection of the Aβ peptide induced misplaced expression of recoverin and synaptophysin in the photoreceptors, oxidative stress in their inner and outer segments, and finally apoptosis. Aβ did not induce cell death in purified photoreceptor cell cultures, but did so in retinal cell cultures, thereby suggesting that the cellular environment plays a role in Aβ-induced photoreceptor apoptosis. Subretinal injection of Aβ was followed by activation and migration of microglial cells and then by photoreceptor apoptosis. Microglial cells phagocytosed rhodopsin-containing debris and Aβ in the subretinal space. Quantitative RT-PCR allowed us to identify a specific gene expression profile associated with the Aβ-induced progression of retinal degeneration and consistent with oxidative stress, inflammation, and an apoptotic program. The gene most highly upregulated in Aβ-injected retinas was that for the chemokine CCL2, and its absence or that of its cognate receptor CCR2 greatly reduced migration of activated microglial cells to the site of retinal injury and profoundly worsened photoreceptor degeneration and disorganization of the retinal pigment epithelium in Aβ-injected retinas. Our study pinpoints the roles of Aβ and of CCL2/CCR2 axis-dependent inflammation in photoreceptor apoptosis. |
topic |
Retina Microglial cells Inflammation Oxidative stress Age-related macular degeneration Alzheimer's disease |
url |
http://www.sciencedirect.com/science/article/pii/S0969996111000052 |
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doaj-d34290eefbef407a85c4d59ec386f7922021-03-22T12:36:22ZengElsevierNeurobiology of Disease1095-953X2011-04-014215572CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosisJulien Bruban0Agathe Maoui1Naïma Chalour2Na An3Laurent Jonet4Charles Feumi5Jacques Tréton6Florian Sennlaub7Francine Behar-Cohen8Frédéric Mascarelli9Virginie Dinet10Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCorresponding author. Centre de Recherche des Cordeliers, UMRS872, 15 rue de l'Ecole de Médecine, 75006 Paris, France. Fax: +33 1 40 46 78 65.; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceCentre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; NSERM, U872, F-75006 Paris, FranceAge-related macular degeneration is characterized by the formation of drusen containing amyloid-β (Aβ) and the degeneration of photoreceptors. To explore the largely unknown role of Aβ in the retina, we investigated the effects on photoreceptors of the oligomeric form of Aβ(1–42). Subretinal injection of the Aβ peptide induced misplaced expression of recoverin and synaptophysin in the photoreceptors, oxidative stress in their inner and outer segments, and finally apoptosis. Aβ did not induce cell death in purified photoreceptor cell cultures, but did so in retinal cell cultures, thereby suggesting that the cellular environment plays a role in Aβ-induced photoreceptor apoptosis. Subretinal injection of Aβ was followed by activation and migration of microglial cells and then by photoreceptor apoptosis. Microglial cells phagocytosed rhodopsin-containing debris and Aβ in the subretinal space. Quantitative RT-PCR allowed us to identify a specific gene expression profile associated with the Aβ-induced progression of retinal degeneration and consistent with oxidative stress, inflammation, and an apoptotic program. The gene most highly upregulated in Aβ-injected retinas was that for the chemokine CCL2, and its absence or that of its cognate receptor CCR2 greatly reduced migration of activated microglial cells to the site of retinal injury and profoundly worsened photoreceptor degeneration and disorganization of the retinal pigment epithelium in Aβ-injected retinas. Our study pinpoints the roles of Aβ and of CCL2/CCR2 axis-dependent inflammation in photoreceptor apoptosis.http://www.sciencedirect.com/science/article/pii/S0969996111000052RetinaMicroglial cellsInflammationOxidative stressAge-related macular degenerationAlzheimer's disease |