title: Deletion of angiotensin II type 1 receptor gene attenuates chronic alcohol-induced retinal ganglion cell death with preservation of VEGF expression.
abstract: OBJECTIVE
  To investigate how chronic alcohol consumption affects adult visual nervous system and whether renin-angiotensin system (RAS) is involved in this pathogenic process.
  
  
  METHODS
  Male transgenic mice with angiotensin II (Ang II) type 1 (AT1) receptor gene knockout (AT1-KO) and age-matched wild-type (WT) mice were pair-fed a modified Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 2 months. At the end of the study, retinas were harvested and subjected to histopathological and immunohistochemical examination.
  
  
  RESULTS
  We found that chronic alcohol consumption significantly increased retinal ganglion cell (RGC) apoptosis in the retina of WT mice, but not AT1-KO mice, detected by terminal deoxynucleotidyl-transferase-mediated dUTP-nick-end labeling staining and caspase 3 activation, along with an up-regulation of AT1 expression in RGC. At the same time, the phosphorylation of P53 in RGCs was significantly increased for both WT and AT1-KO mice exposed to alcohol, which could be significantly, although partially, prevented by AT1 gene deletion. We further examined the expression of vascular endothelial growth factor (VEGF) and CD31, and found that alcohol treatment significantly decreased the expression of VEGF and CD31 in RGCs of WT mice, but not AT1-KO mice.
  
  
  CONCLUSIONS
  Taken together, our study demonstrates that the induction of RGC apoptosis by chronic alcohol exposure may be related to p53-activation and VEGF depression, all which are partially dependent of AT1 receptor activation.
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, Changchun, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Miao
authors.forename: Huayi
authors.initials: H
authors.lastname: Lv
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Lining
authors.initials: L
authors.lastname: Miao
authors.forename: Guanfang
authors.initials: G
authors.lastname: Su
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D042461:Vascular Endothelial Growth Factor A; D000431:Ethanol