CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis

Neurobiology of Disease

Naïma Chalour¹  Francine Behar-Cohen¹  Charles Feumi¹  Virginie Dinet²  Florian Sennlaub²  Laurent Jonet²  Agathe Maoui²  Jacques Tréton³  Julien Bruban³  Frédéric Mascarelli³  Na An³ 

[1] NSERM, U872, F-75006 Paris, France;Université Paris Descartes, UMR S 872, F-75006 Paris, France;Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMRS 872, F-75006 Paris, France;

关键词: Retina;    Microglial cells;    Inflammation;    Oxidative stress;    Age-related macular degeneration;    Alzheimer's disease;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown