title: Hyperoxia causes regression of vitreous neovascularization by downregulating VEGF/VEGFR2 pathway.
abstract: OBJECTIVE
  Neovascularization (NV) is a sight-threatening complication of retinal ischemia in diabetes, retinal vein occlusion, and retinopathy of prematurity. Current treatment modalities, including laser photocoagulation and repeated intraocular injection of VEGF antagonists, are invasive and not always effective, and may carry side effects. We studied the use of hyperoxia as an alternative therapeutic strategy for regressing established vitreous NV in a mouse model of oxygen-induced ischemic retinopathy.
  
  
  METHODS
  Hyperoxia treatment (HT, 75% oxygen) was initiated on postnatal day (P)17 after the onset of vitreous NV. Immunohistochemistry and quantitative PCR were used to assess retinal vascular changes in relation to apoptosis, and expression of VEGFR2 and inflammatory molecules. Effects of intravitreal injections of VEGF-A, VEGF-E, PlGF-1, and VEGF trap were also studied.
  
  
  RESULTS
  HT selectively reduced NV by 70% within 24 hours. It robustly increased the level of cleaved caspase-3 in the vitreous NV between 6 and 18 hours and promoted infiltration of macrophage/microglial cells. The HT-induced apoptosis was preceded by a significant reduction in VEGFR2 expression within the NV and an increase in VEGFR2 within the surrounding neural tissue. Intravitreal VEGF-A and VEGF-E (VEGFR2 agonist) but not PlGF-1 (VEGFR1 agonist) prevented HT-induced apoptosis and regression of NV. In contrast, VEGF trap and VEGFR2 blockers mimicked the effect of HT. However, intravitreal VEGF trap induced increases in inflammatory molecules while HT did not have such unwanted effect.
  
  
  CONCLUSIONS
  HT may be clinically useful to specifically treat proliferative NV in ischemic retinopathy.
authors: Vascular Biology Center, Georgia Health Sciences University, Augusta, USA.
authors: Hua
authors: H
authors: Liu
authors: Wenbo
authors: W
authors: Zhang
authors: Zhimin
authors: Z
authors: Xu
authors: Robert W
authors: RW
authors: Caldwell
authors: Ruth B
authors: RB
authors: Caldwell
authors: Steven E
authors: SE
authors: Brooks
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D005128:Eye Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics*; D014822:Vitreous Body / Q000098:blood supply* / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen