PMID- 24586862
OWN - NLM
STAT- MEDLINE
DCOM- 20150303
LR  - 20220129
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - RAGE regulates immune cell infiltration and angiogenesis in choroidal 
      neovascularization.
PG  - e89548
LID - 10.1371/journal.pone.0089548 [doi]
LID - e89548
AB  - PURPOSE: RAGE regulates pro-inflammatory responses in diverse cells and tissues. 
      This study has investigated if RAGE plays a role in immune cell mobilization and 
      choroidal neovascular pathology that is associated with the neovascular form of 
      age-related macular degeneration (nvAMD). METHODS: RAGE null (RAGE-/-) mice and 
      age-matched wild type (WT) control mice underwent laser photocoagulation to 
      generate choroidal neovascularization (CNV) lesions which were then analyzed for 
      morphology, S100B immunoreactivity and inflammatory cell infiltration. The 
      chemotactic ability of bone marrow derived macrophages (BMDMs) towards S100B was 
      investigated. RESULTS: RAGE expression was significantly increased in the retina 
      during CNV of WT mice (p<0.001). RAGE-/- mice exhibited significantly reduced CNV 
      lesion size when compared to WT controls (p<0.05). S100B mRNA was upregulated in 
      the lasered WT retina but not RAGE-/- retina and S100B immunoreactivity was 
      present within CNV lesions although levels were less when RAGE-/- mice were 
      compared to WT controls. Activated microglia in lesions were considerably less 
      abundant in RAGE-/- mice when compared to WT counterparts (p<0.001). A dose 
      dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05-0.01) 
      but this was not apparent in cells isolated from RAGE-/- mice. CONCLUSIONS: 
      RAGE-S100B interactions appear to play an important role in CNV lesion formation 
      by regulating pro-inflammatory and angiogenic responses. This study highlights 
      the role of RAGE in inflammation-mediated outer retinal pathology.
FAU - Chen, Mei
AU  - Chen M
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Glenn, Josephine V
AU  - Glenn JV
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Dasari, Shilpa
AU  - Dasari S
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - McVicar, Carmel
AU  - McVicar C
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Ward, Michael
AU  - Ward M
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Colhoun, Liza
AU  - Colhoun L
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Quinn, Michael
AU  - Quinn M
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Bierhaus, Angelika
AU  - Bierhaus A
AD  - Department of Medicine and Clinical Chemistry, University of Heidelberg, 
      Heidelberg, Germany.
FAU - Xu, Heping
AU  - Xu H
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
FAU - Stitt, Alan W
AU  - Stitt AW
AD  - Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United 
      Kingdom.
LA  - eng
GR  - G0801962/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140226
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (S100 Calcium Binding Protein beta Subunit)
RN  - 0 (S100b protein, mouse)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemotaxis
MH  - Choroidal Neovascularization/*immunology/metabolism/pathology
MH  - Disease Models, Animal
MH  - Macrophages/immunology/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neovascularization, Pathologic/*immunology/metabolism/pathology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*physiology
MH  - Retina/*immunology/metabolism/pathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - S100 Calcium Binding Protein beta Subunit/genetics/*metabolism
PMC - PMC3935881
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/04 06:00
MHDA- 2015/03/04 06:00
PMCR- 2014/02/26
CRDT- 2014/03/04 06:00
PHST- 2013/09/30 00:00 [received]
PHST- 2014/01/23 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2015/03/04 06:00 [medline]
PHST- 2014/02/26 00:00 [pmc-release]
AID - PONE-D-13-39938 [pii]
AID - 10.1371/journal.pone.0089548 [doi]
PST - epublish
SO  - PLoS One. 2014 Feb 26;9(2):e89548. doi: 10.1371/journal.pone.0089548. eCollection 
      2014.