Activating the Wnt/β-catenin pathway did not protect immature retina from hypoxic-ischemic injury

Hsiu Mei Huang, Chao Ching Huang, Feng Sheng Wang, Pi Liang Hung, Ying Chao Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations


PURPOSE. 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.

Original languageEnglish
Pages (from-to)4300-4308
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number8
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.


  • DKK-1
  • Hypoxic-ischemia
  • Lithium
  • Retinal injury
  • Wnt/β-catenin


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