title: Effects of anti-VEGF treatment on the recovery of the developing retina following oxygen-induced retinopathy.
abstract: OBJECTIVE
  Inhibition of VEGF is widely used in patients to control neovascularization and decrease vascular permeability. To date, the effect of VEGF inhibition has not been evaluated in the developing retina such as that seen in premature infants. The goal of this study was to address the effect of anti-VEGF treatment on retinal development of a mouse model of retinopathy.
  
  
  METHODS
  C57BL/6J mice were evaluated using a model of oxygen-induced retinopathy. Test animals were treated at postnatal day (P) 14 with intravitreal injections of the VEGF inhibitor aflibercept (2.5 or 10 μg) in one eye. Control animals were treated with injection of PBS in one eye. The noninjected fellow eyes were used as internal controls. Areas of avascular retina and neovascular tufts in injected (treated) eyes and noninjected fellow eyes were determined at P17, and the difference related to these characteristics was obtained among them. To evaluate the effect of VEGF inhibition on neurogenesis, focal ERG was performed at P21 and P42. Histologic evaluation of the retinal structure was also evaluated at P42.
  
  
  RESULTS
  Aflibercept treatment reduced the amount of neovascular tufts but significantly increased the area of avascular retina (low dose and high dose) at P17. The delayed vascular growth corresponded to decreased ERG amplitudes (at P21 and P42) and structural changes in the retinal layers that persisted (at P42), despite vascular recovery.
  
  
  CONCLUSIONS
  Inhibition of VEGF in developing eyes has the short-term effect of delayed vascular growth and the long-term effects of decreased function with persistent changes in the neuroretinal structures.
authors.affiliation: Pediatric Retinal Research Laboratory, Eye Research Institute, Oakland University, Rochester, Michigan.
authors.forename: Clayton C
authors.initials: CC
authors.lastname: Tokunaga
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Mitton
authors.forename: Wendelin
authors.initials: W
authors.lastname: Dailey
authors.forename: Charlotte
authors.initials: C
authors.lastname: Massoll
authors.forename: Kevin
authors.initials: K
authors.lastname: Roumayah
authors.forename: Ed
authors.initials: E
authors.lastname: Guzman
authors.forename: Noor
authors.initials: N
authors.lastname: Tarabishy
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Drenser
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004596:Electroretinography; D005500:Follow-Up Studies; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects*; D012160:Retina / Q000502:physiology*; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D010100:Oxygen
keywords: VEGF; aflibercept; anti-VEGF; neurovascular niche; retinopathy of prematurity