title: Aldose reductase deficiency reduced vascular changes in neonatal mouse retina in oxygen-induced retinopathy.
abstract: OBJECTIVE
  Retinal neovascularization is the major pathologic process in many ocular diseases and is associated with oxidative stress. Deficiency of aldose reductase (AR), the first enzyme in the polyol pathway for glucose metabolism, has been shown to reduce oxidative stress and blood vessel leakage. The present study aimed to investigate the effect of AR deficiency on retinal neovascularization in a murine oxygen-induced retinopathy (OIR) model.
  
  
  METHODS
  Seven-day-old wild-type (WT) and AR-deficient (AR(-/-)) mice were exposed to 75% oxygen for 5 days and then returned to room air. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. Immunohistochemistry for AR, nitrotyrosine (NT), poly(ADP-ribose) (PAR), glial fibrillary acidic protein (GFAP), and Iba-1, as well as Western blots for vascular endothelial growth factor (VEGF), phospho-Erk (p-Erk), phospho-Akt (p-Akt), and phospho-IκB (p-IκB) were performed.
  
  
  RESULTS
  Compared with WT OIR retinae, AR(-/-) OIR retinae displayed significantly smaller central retinal vaso-obliterated area, less neovascularization, and reduced blood vessel leakage. Significantly reduced oxidative stress and glial responses were also observed in AR(-/-) OIR retinae. Moreover, reduced microglial response in the avascular area but increased microglial responses in the neovascular area were found with AR deficiency. Furthermore, expression levels of VEGF, p-Erk, p-Akt, and p-IκB were significantly reduced in AR(-/-) OIR retinae.
  
  
  CONCLUSIONS
  Our observations indicated that AR deficiency reduced retinal vascular changes in the mouse model of OIR, indicating that AR can be a potential therapeutic target in ischemia-induced retinopathy.
authors: Eye Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors: Zhong Jie
authors: ZJ
authors: Fu
authors: Suk-Yee
authors: SY
authors: Li
authors: Norbert
authors: N
authors: Kociok
authors: David
authors: D
authors: Wong
authors: Sookja K
authors: SK
authors: Chung
authors: Amy C Y
authors: AC
authors: Lo
mesh_terms: D000449:Aldehyde Reductase / Q000172:deficiency*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002199:Capillary Permeability; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007231:Infant, Newborn; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015861:Retinal Neovascularization / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D020672:I-kappa B Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D042461:Vascular Endothelial Growth Factor A; C528900:glial fibrillary astrocytic protein, mouse; C467480:vascular endothelial growth factor A, mouse; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D000449:Aldehyde Reductase; D051057:Proto-Oncogene Proteins c-akt; D010100:Oxygen