Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0160985
Title: Choroidal neovascularization is inhibited in splenic-denervated or splenectomized mice with a concomitant decrease in intraocular macrophage
Authors: Tan X.
Fujiu K.
Manabe I.
Nishida J.
Yamagishi R.
Terashima Y.
Matsushima K.
Kaburaki T.
Nagai R.
Yanagi Y. 
Keywords: beta 3 adrenergic receptor blocking agent
clodronic acid
Ccr2 protein, mouse
chemokine receptor CCR2
Ly antigen
Ly-6C antigen, mouse
adoptive transfer
animal cell
animal experiment
animal model
animal tissue
Article
CD4+ T lymphocyte
CD8+ T lymphocyte
controlled study
denervation
disease course
granulocyte
laser
lymphocyte
macrophage
male
monocyte
mouse
nonhuman
pathogenesis
splenectomy
splenic denervation
subretinal neovascularization
animal
C57BL mouse
cell motion
Choroidal Neovascularization
classification
deficiency
disease model
eye
genetics
immunology
innervation
knockout mouse
macrophage
metabolism
pathology
spleen
splenectomy
sympathectomy
Adoptive Transfer
Animals
Antigens, Ly
Cell Movement
Choroidal Neovascularization
Disease Models, Animal
Eye
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, CCR2
Spleen
Splenectomy
Sympathectomy
Issue Date: 2016
Citation: Tan X., Fujiu K., Manabe I., Nishida J., Yamagishi R., Terashima Y., Matsushima K., Kaburaki T., Nagai R., Yanagi Y. (2016). Choroidal neovascularization is inhibited in splenic-denervated or splenectomized mice with a concomitant decrease in intraocular macrophage. PLoS ONE 11 (8) : e0160985. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0160985
Rights: Attribution 4.0 International
Abstract: Purpose: To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. Methods: 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 ?3 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. Results: 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 ?3 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. Conclusions: 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. © 2016 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161562
ISSN: 19326203
DOI: 10.1371/journal.pone.0160985
Rights: Attribution 4.0 International
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This item is licensed under a Creative Commons License Creative Commons