Eandi Chiara M, Charles Messance Hugo, Augustin Sébastien, Dominguez Elisa, Lavalette Sophie, Forster Valérie, Hu Shulong Justin, Siquieros Lourdes, Craft Cheryl Mae, Sahel José-Alain, Tadayoni Ramin, Paques Michel, Guillonneau Xavier, Sennlaub Florian
Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.
Institut de la Vision, Paris, France.
Elife. 2016 Jul 20;5:e16490. doi: 10.7554/eLife.16490.
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.
视锥细胞节段（CS）中的光转导对于高敏锐度的日间视觉至关重要。由于不明原因，视锥细胞节段在视网膜色素变性（RP）以及作为地图样萎缩（GA）特征的萎缩区（AZ）的过渡区（TZ）中发生退化。我们的实验证实了GA患者过渡区中视锥细胞节段的丧失，并表明它们与视网膜下CD14(+)单核吞噬细胞（MP）浸润有关，RP中也有这种浸润的报道。利用体外的人和小鼠单核吞噬细胞以及体内易发生炎症的Cx3cr1(GFP/GFP)小鼠，我们证明单核吞噬细胞衍生的白细胞介素-1β会导致严重的视锥细胞节段退化。我们的结果强烈表明，视网膜下单核吞噬细胞的积累参与了这些疾病中观察到的病理性光感受器变化。抑制视网膜下单核吞噬细胞的积累或白细胞介素-1β可能会保护视锥细胞节段，并有助于在以视网膜下炎症为特征的疾病（如年龄相关性黄斑变性和视网膜色素变性）中保留高敏锐度的日间视觉。
