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Hsiu-Mei Huang, Chao-Ching Huang, Feng-Sheng Wang, Pi-Liang Hung, Ying-Chao Chang; Activating the Wnt/β-Catenin Pathway Did Not Protect Immature Retina from Hypoxic-Ischemic Injury. Invest. Ophthalmol. Vis. Sci. 2015;56(8):4300-4308. doi: 10.1167/iovs.14-16176.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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).
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.
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.
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