Subretinal mononuclear phagocytes induce cone segment loss via IL-1β
Subretinal mononuclear phagocytes induce cone segment loss via IL-1β
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DOI：
10.7554/elife.16490
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发表时间：
2016-07-20
期刊：
影响因子：
7.7
通讯作者：
Sennlaub, Florian
中科院分区：
文献类型：
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作者：
Eandi, Chiara M.;Messance, Hugo Charles;Sennlaub, Florian
视锥细胞节段（CS）中的光传导对于白天高视力至关重要。由于不明确的原因，CS在视网膜色素变性（RP）和萎缩区（AZ）的过渡区（TZ）中退化，这是地图状萎缩（GA）的特征。我们的实验证实了GA患者TZ区的视锥细胞节段（CS）缺失，并显示了它们与视网膜下CD 14（+）单核吞噬细胞（MP）浸润的相关性，这也在RP中报道。使用人和小鼠MP在体外和炎症易感Cx 3cr 1（GFP/GFP）小鼠在体内，我们证明，MP衍生的IL-1 β导致严重的CS变性。我们的研究结果强烈表明，视网膜下MP积累参与了这些疾病中观察到的病理性感光细胞变化。抑制视网膜下MP积聚或IL-1 β可能保护CS，并有助于在以视网膜下炎症为特征的疾病（如AMD和RP）中保持高敏锐度日间视力。
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-1 beta 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-1 beta might protect the CS and help preserve high acuity daytime vision in conditions characterized by subretinal inflammation, such as AMD and RP.