title: Activating the Wnt/β-Catenin Pathway Did Not Protect Immature Retina from Hypoxic-Ischemic Injury.
abstract: OBJECTIVE
  Visual loss associated with hypoxic-ischemic (HI) brain damage is the most common cause of visual impairment in children of developed countries. A neuroprotective role for Wnt/β-catenin signaling has been demonstrated in several neurodegenerative disorders. The association of Wnt signaling with HI injury in immature retina has not been established.
  
  
  METHODS
  On postnatal day 7 (P7), HI was induced by unilateral common carotid artery ligation followed by 8% oxygen hypoxia for 2 hours. The pups received intravitreous injection (i.v.i) of PBS, Dickkopf-1 (DKK-1, the negative modulator of Wnt/β-catenin pathway) antisense (AS) or sense (S) oligonucleotides at various concentrations for pretreatment (24 and 1 hour before HI) or post treatment (1 and 4 hours after HI). For chronic treatments, animals received repeated intraperitoneal (i.p.) injection of DKK-1-AS, DKK-1-S, lithium chloride (LiCl), or vehicles after HI. The retinal injury was assessed by electroretinography (ERG, P21, and P30) and immunohistochemical staining (P8 or P30).
  
  
  RESULTS
  Pretreatment with DKK-1-AS (i.v.i.) attenuated DKK-1 and enhanced β-catenin expression, but did not protect immature retina against HI injury at both pathological and functional levels. Post treatment with DKK-1-AS (i.v.i. or i.p.) also did not rescue HI retinopathy. Chronic systemic LiCl treatment did not decrease Müller cell activation or neuronal damage in HI retinal injury.
  
  
  CONCLUSIONS
  Our data demonstrated that DKK-1 inhibition or chronic lithium treatment did not protect the immature retina from HI injury. It is speculated that the enhanced canonical Wnt/β-catenin signaling is not sufficient to protect the immature retina from HI injury.
authors.affiliation: Department of Ophthalmology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, National Cheng Kung University Hospital, Tainan City, Taiwan and Department of Pediatrics, Taipei Medical University, College of Medicine, Taipei, Taiwan.
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Feng-Sheng
authors.initials: FS
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Pi-Liang
authors.initials: PL
authors.lastname: Hung
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D016923:Cell Death; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin