title: Retinal vascular rescue of oxygen-induced retinopathy in mice by norrin.
abstract: OBJECTIVE
  Wnt-signaling has been implicated in retinal development. The aim of this study was to investigate the possibility of improving retinal vasculature in an animal model of retinopathy by activating Wnt-signaling.
  
  
  METHODS
  C57BL/6J mice were evaluated using a model of oxygen-induced retinopathy (OIR). Test animals were divided in three groups and treated at postnatal day (P) 14 with intravitreal injections of Wnt-signaling modulators (respectively, norrin, Dickkopf-related protein 1 [DKK1], and norrin + DKK1) in one eye. A fourth group of animals were treated with injection of PBS in one eye as well and used as a control group. Areas of avascular retina and neovascular tufts in injected (treated) eyes and noninjected fellow eyes were determined in each of the four groups at P17 (3 days after intravitreal injection) and the difference related to these characteristics was obtained among them. To evaluate the effect of norrin on progression of retinopathy, a fifth litter (eight animals) was also treated with norrin and these retinas were evaluated at different time points.
  
  
  RESULTS
  Modulation of Wnt-signaling consistently shows a statistically significant decrease in the avascular area of the retinas. Treatment with norrin (Wnt-signaling activator) or DKK1 (canonical signaling inhibitor) results in a statistically significant reduction of retinal avascular area compared with control eyes. Neovascular tufts were also reduced in treated eyes, albeit to a lesser extent.
  
  
  CONCLUSIONS
  Modulation of Wnt-signaling improves retinal vascularization and accelerates vascular recovery after induction of retinopathy in the OIR mouse. Activation of Wnt-signaling (norrin) and inhibition of Wnt-canonical signaling (DKK1) result in similar improvement, indicating that norrin promotes improved vascularization, at least in part, by way of noncanonical Wnt-signaling.
authors.affiliation: Eye Research Institute, Oakland University, Rochester, Michigan 48309-4401, USA.
authors.forename: Clayton C
authors.initials: CC
authors.lastname: Tokunaga
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Chen
authors.forename: Wendelin
authors.initials: W
authors.lastname: Dailey
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; D001835:Body Weight; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D058449:Intravitreal Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010100:Oxygen / Q000009:adverse effects; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
chemical_list: C501127:Dkk1 protein, mouse; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; C489916:Ndph protein, mouse; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; D010100:Oxygen