title: RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization.
abstract: OBJECTIVE
  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.
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Josephine V
authors.initials: JV
authors.lastname: Glenn
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Carmel
authors.initials: C
authors.lastname: McVicar
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Ward
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Liza
authors.initials: L
authors.lastname: Colhoun
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Quinn
authors.affiliation: Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Heping
authors.initials: H
authors.lastname: Xu
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002633:Chemotaxis; D020256:Choroidal Neovascularization / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D012160:Retina / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse