RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization

Chen, Mei, Glenn, Josephine V., Dasari, Shilpa, McVicar, Carmel, Ward, Michael, Colhoun, Liza, Quinn, Michael, Bierhaus, Angelika, Xu, Heping and Stitt, Alan W. (2014) RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization. PLoS One, 9 2: e89548-e89548. doi:10.1371/journal.pone.0089548


Author Chen, Mei
Glenn, Josephine V.
Dasari, Shilpa
McVicar, Carmel
Ward, Michael
Colhoun, Liza
Quinn, Michael
Bierhaus, Angelika
Xu, Heping
Stitt, Alan W.
Title RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-02-26
Sub-type Article (original research)
DOI 10.1371/journal.pone.0089548
Open Access Status DOI
Volume 9
Issue 2
Start page e89548
End page e89548
Total pages 11
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2015
Language eng
Abstract 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 agerelated 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 proinflammatory and angiogenic responses. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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