title: Subretinal mononuclear phagocytes induce cone segment loss via IL-1β.
abstract: Photo-transduction in cone segments (CS) is crucial for high acuity daytime vision. For ill-defined reasons, CS degenerate in retinitis pigmentosa (RP) and in the transitional zone (TZ) of atrophic zones (AZ), which characterize geographic atrophy (GA). Our experiments confirm the loss of cone segments (CS) in the TZ of patients with GA and show their association with subretinal CD14(+)mononuclear phagocyte (MP) infiltration that is also reported in RP. Using human and mouse MPs in vitro and inflammation-prone Cx3cr1(GFP/GFP) mice in vivo, we demonstrate that MP-derived IL-1β leads to severe CS degeneration. Our results strongly suggest that subretinal MP accumulation participates in the observed pathological photoreceptor changes in these diseases. Inhibiting subretinal MP accumulation or Il-1β might protect the CS and help preserve high acuity daytime vision in conditions characterized by subretinal inflammation, such as AMD and RP.
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.|Department of Clinical Science, University of Torino, Torino, Italy.|Eye Clinic, University of Torino, Torino, Italy.
authors.forename: Chiara M
authors.identifier: 0000-0003-3656-1689
authors.initials: CM
authors.lastname: Eandi
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Charles Messance
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Augustin
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dominguez
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavalette
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Forster
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Shulong Justin
authors.initials: SJ
authors.lastname: Hu
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Siquieros
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Keck School of Medicine of the University of Southern California, Los Angeles, United States.|University of Southern California Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, United States.|Department of Ophthalmology and Cell, Keck School of Medicine of the University of Southern California, Los Angeles, United States.|Department of Neurobiology, Keck School of Medicine of the University of Southern California, Los Angeles, United States.
authors.forename: Cheryl Mae
authors.initials: CM
authors.lastname: Craft
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.|Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.|Department of Ophthalmology, Hôpital Lariboisièr, Paris, France.
authors.forename: Ramin
authors.initials: R
authors.lastname: Tadayoni
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.|Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Paques
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Xavier
authors.identifier: 0000-0001-7379-3935
authors.initials: X
authors.lastname: Guillonneau
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.|Institut de la Vision, Paris, France.
authors.forename: Florian
authors.identifier: 0000-0003-4412-1341
authors.initials: F
authors.lastname: Sennlaub
mesh_terms: D000818:Animals; D057092:Geographic Atrophy / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D010586:Phagocytes / Q000276:immunology*; D012160:Retina / Q000473:pathology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta
keywords: age-related macular degeneration; human; human biology; interleukin; macrophages; medicine; mouse; neuroscience; outer segments; retinitis pigmentosa; subretinal space