title: Role of the receptor for advanced glycation endproducts (RAGE) in retinal vasodegenerative pathology during diabetes in mice.
abstract: OBJECTIVE
  The receptor for AGEs (RAGE) is linked to proinflammatory pathology in a range of tissues. The objective of this study was to assess the potential modulatory role of RAGE in diabetic retinopathy.
  
  
  METHODS
  Diabetes was induced in wild-type (WT) and Rage (-/-) mice (also known as Ager (-/-) mice) using streptozotocin while non-diabetic control mice received saline. For all groups, blood glucose, HbA1c and retinal levels of methylglyoxal (MG) were evaluated up to 24 weeks post diabetes induction. After mice were killed, retinal glia and microglial activation, vasopermeability, leucostasis and degenerative microvasculature changes were determined.
  
  
  RESULTS
  Retinal expression of RAGE in WT diabetic mice was increased after 12 weeks (p < 0.01) but not after 24 weeks. Rage (-/-) mice showed comparable diabetes but accumulated less MG and this corresponded to enhanced activity of the MG-detoxifying enzyme glyoxalase I in their retina when compared with WT mice. Diabetic Rage (-/-) mice showed significantly less vasopermeability, leucostasis and microglial activation (p < 0.05-0.001). Rage (-/-) mice were also protected against diabetes-related retinal acellular capillary formation (p < 0.001) but not against pericyte loss.
  
  
  CONCLUSIONS
  Rage (-/-) in diabetic mice is protective against many retinopathic lesions, especially those related to innate immune responses. Inhibition of RAGE could be a therapeutic option to prevent diabetic retinopathy.
authors: Centre for Experimental Medicine, Queen's University Belfast, Belfast, BT12 6BA, Northern Ireland, UK.
authors: Carmel M
authors: CM
authors: McVicar
authors: Micheal
authors: M
authors: Ward
authors: Liza M
authors: LM
authors: Colhoun
authors: Jasenka
authors: J
authors: Guduric-Fuchs
authors: Angelika
authors: A
authors: Bierhaus
authors: Thomas
authors: T
authors: Fleming
authors: Andreas
authors: A
authors: Schlotterer
authors: Matthias
authors: M
authors: Kolibabka
authors: Hans-Peter
authors: HP
authors: Hammes
authors: Mei
authors: M
authors: Chen
authors: Alan W
authors: AW
authors: Stitt
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D018921:Leukostasis / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D011765:Pyruvaldehyde / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology
chemical_list: D001786:Blood Glucose; D000067759:Receptor for Advanced Glycation End Products; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase