c-Abl is required for the development of hyperoxia-induced retinopathy

Irene Nunes, Rosemary D. Higgins, Lucia Zanetta, Peter Shamamian, Stephen P. Goff

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The requirement for the nonreceptor tyrosine kinase c-abl in the pathogenesis of retinopathy of prematurity (ROP) was examined using the mouse model for ROP and c-abl-deficient mice. Hyperoxia-induced retinal neovascularization was observed in wild-type and heterozygous mice but animals that were homozygous null for c-abl did not develop a vasoproliferative retinopathy in response to hyperoxia. Two gene products, endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF), have been implicated in the pathogenesis of ROP. The mRNA expression of ET-1 and VEGF was assessed in mice maintained in normoxia and in hyperoxia-exposed mice. ET-1 mRNA levels were unchanged in wild-type mice throughout the hyperoxia treatment, suggesting that ET-1 mRNA expression is not regulated by the increase in inspired oxygen. In wild-type mice maintained in room air, VEGF mRNA levels rose threefold from postnatal day 6 (P6) to P17. When wild-type mice were treated with the hyperoxia regimen, a fivefold decrease in VEGF mRNA expression was observed from P7 to P16. However, retinal VEGF expression in hyperoxia-treated homozygous null mice did not decrease and remained at control levels. These data suggest that c-abl is required for the hyperoxia-induced retinal neovascularization and hyperoxia-induced decrease in VEGF mRNA levels.

Original languageEnglish (US)
Pages (from-to)1383-1391
Number of pages9
JournalJournal of Experimental Medicine
Volume193
Issue number12
DOIs
StatePublished - Jun 18 2001
Externally publishedYes

Fingerprint

Hyperoxia
Vascular Endothelial Growth Factor A
Endothelin-1
Retinopathy of Prematurity
Messenger RNA
Retinal Neovascularization
Protein-Tyrosine Kinases
Air
Oxygen

Keywords

  • DNA damage
  • Nonreceptor tyrosine kinase
  • Oxidative stress
  • Retinal angiogenesis
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Immunology

Cite this

c-Abl is required for the development of hyperoxia-induced retinopathy. / Nunes, Irene; Higgins, Rosemary D.; Zanetta, Lucia; Shamamian, Peter; Goff, Stephen P.

In: Journal of Experimental Medicine, Vol. 193, No. 12, 18.06.2001, p. 1383-1391.

Research output: Contribution to journalArticle

Nunes, Irene ; Higgins, Rosemary D. ; Zanetta, Lucia ; Shamamian, Peter ; Goff, Stephen P. / c-Abl is required for the development of hyperoxia-induced retinopathy. In: Journal of Experimental Medicine. 2001 ; Vol. 193, No. 12. pp. 1383-1391.
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