Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage.
Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage.
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DOI：
10.1371/journal.pone.0160985
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yanagi Y
中科院分区：
文献类型：
--
作者：
Tan X;Fujiu K;Manabe I;Nishida J;Yamagishi R;Terashima Y;Matsushima K;Kaburaki T;Nagai R;Yanagi Y
通过激光诱导脉络膜新生血管（CNV）的小鼠模型，研究交感神经活动在CNV中的作用。我们使用流式细胞术研究了小鼠激光损伤后眼内淋巴细胞、粒细胞和三种巨噬细胞亚型（Ly 6 Chi、Ly 6 Cint和Ly 6 Clo）的比例变化，并评估了缺乏炎症细胞的小鼠中CNV病变大小。此外，我们评估了给予β3受体拮抗剂的小鼠、去脾神经支配的小鼠和脾切除的小鼠的病变大小。我们还评估了去脾神经和脾切除小鼠眼内巨噬细胞和外周血单核细胞比例的变化。最后，比较了激光损伤后有或没有巨噬细胞过继转移的去脾神经小鼠之间的病变大小。将Ly5.1小鼠脾来源的Ly 6Chi细胞转移到Ly5.2小鼠中后，比较眼内Ly5.1+ Ly 6Chi细胞的比例。在WT小鼠中，从激光损伤后第3天到第7天，募集到眼内的CD 4 + T细胞的比例逐渐增加，而眼内CD 8 + T细胞没有显著变化。B220+细胞、粒细胞和两种眼内巨噬细胞亚型（Ly 6Chi和Ly 6Clo）的比例在激光损伤后第3天达到峰值。相比之下，Ly 6Cint/loCD 64+亚型在激光损伤后第7天显示出显著更高的百分比。CD 4-/-或Rag 2-/-小鼠和对照组之间的病变大小没有差异，而CCR 2 −/−小鼠和氯膦酸盐脂质体治疗小鼠的病变大小显著减少。与对照组相比，β3受体阻滞剂治疗组、去脾神经组和脾切除组小鼠的CNV病变面积显著减少。眼内Ly 6Chi巨噬细胞也减少脾去神经支配或脾切除术。脾来源的Ly 6Chi细胞的连续转移增加了脾去神经小鼠的病变大小。与对照组相比，眼内供体来源的Ly 6Chi细胞在脾去神经和脾切除小鼠中被招募到眼睛中减少。虽然淋巴细胞对CNV的形成几乎没有影响，但Ly 6Chi巨噬细胞/单核细胞加重了小鼠的CNV。交感神经活性可能通过将巨噬细胞募集到眼睛而促成CNV。
To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared. In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4–/–or Rag2–/–mice and controls, whereas lesion size was significantly reduced in CCR2−/− mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice. Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.