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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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
Volume56
Issue number8
DOIs
Publication statusPublished - 2015

Fingerprint

Catenins
Wnt Signaling Pathway
Retina
Wounds and Injuries
Lithium Chloride
Intraperitoneal Injections
Electroretinography
Therapeutics
Brain Hypoxia
Injections
Common Carotid Artery
Vision Disorders
Lithium
Developed Countries
Oligonucleotides
Neurodegenerative Diseases
Ligation
Staining and Labeling
Oxygen

Keywords

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

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Activating the Wnt/β-catenin pathway did not protect immature retina from hypoxic-ischemic injury. / Huang, Hsiu Mei; Huang, Chao Ching; Wang, Feng Sheng; Hung, Pi Liang; Chang, Ying Chao.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 8, 2015, p. 4300-4308.

Research output: Contribution to journalArticle

Huang, Hsiu Mei ; Huang, Chao Ching ; Wang, Feng Sheng ; Hung, Pi Liang ; Chang, Ying Chao. / Activating the Wnt/β-catenin pathway did not protect immature retina from hypoxic-ischemic injury. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 8. pp. 4300-4308.
@article{9d0df22352f84682a916e2c1074f40be,
title = "Activating the Wnt/β-catenin pathway did not protect immature retina from hypoxic-ischemic injury",
abstract = "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 M{\"u}ller 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.",
keywords = "DKK-1, Hypoxic-ischemia, Lithium, Retinal injury, Wnt/β-catenin",
author = "Huang, {Hsiu Mei} and Huang, {Chao Ching} and Wang, {Feng Sheng} and Hung, {Pi Liang} and Chang, {Ying Chao}",
year = "2015",
doi = "10.1167/iovs.14-16176",
language = "English",
volume = "56",
pages = "4300--4308",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "8",

}

TY - JOUR

T1 - Activating the Wnt/β-catenin pathway did not protect immature retina from hypoxic-ischemic injury

AU - Huang, Hsiu Mei

AU - Huang, Chao Ching

AU - Wang, Feng Sheng

AU - Hung, Pi Liang

AU - Chang, Ying Chao

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - DKK-1

KW - Hypoxic-ischemia

KW - Lithium

KW - Retinal injury

KW - Wnt/β-catenin

UR - http://www.scopus.com/inward/record.url?scp=84939612537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939612537&partnerID=8YFLogxK

U2 - 10.1167/iovs.14-16176

DO - 10.1167/iovs.14-16176

M3 - Article

VL - 56

SP - 4300

EP - 4308

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 8

ER -