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c-abl is required for the development of hyperoxia-induced retinopathy.

Nunes I, Higgins RD, Zanetta L, Shamamian P, Goff SP - J. Exp. Med. (2001)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

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 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 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.

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Corneal angiogenesis assay of wt and c-abl–deficient mice. VEGF-saturated or PBS sham Hydron pellets were implanted in corneas of 3-wk-old mice and 7 d postimplantation corneas were examined using slit-lamp biomicroscopy.
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Figure 5: Corneal angiogenesis assay of wt and c-abl–deficient mice. VEGF-saturated or PBS sham Hydron pellets were implanted in corneas of 3-wk-old mice and 7 d postimplantation corneas were examined using slit-lamp biomicroscopy.

Mentions: Because VEGF is involved in the development of hyperoxia-induced retinal vasoproliferation 5 and mice deficient in c-abl failed to develop hyperoxia-induced retinopathy, we sought to determine if mice that lack c-abl could respond normally to VEGF. To examine if homozygous c-abl mice generate an angiogenic response to exogenously supplied VEGF, a corneal angiogenesis assay was employed 35. A PBS sham or VEGF-saturated Hydron pellet was implanted surgically in corneas of 3-wk-old wt and homozygous mice. New blood vessels emerged from the limbal vasculature of wt and c-abl−/− mice toward the VEGF-saturated pellet, whereas no vessels were observed in animals with sham pellets (Fig. 5). The density of angiogenic vessels emerging from the limbus toward the pellet was similar between +/+ and −/− mice. These observations demonstrate that c-abl activity is not required for VEGF-induced signal transduction and that the c-abl−/− mice responded normally to the ectopic administration of VEGF.


c-abl is required for the development of hyperoxia-induced retinopathy.

Nunes I, Higgins RD, Zanetta L, Shamamian P, Goff SP - J. Exp. Med. (2001)

Corneal angiogenesis assay of wt and c-abl–deficient mice. VEGF-saturated or PBS sham Hydron pellets were implanted in corneas of 3-wk-old mice and 7 d postimplantation corneas were examined using slit-lamp biomicroscopy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193304&req=5

Figure 5: Corneal angiogenesis assay of wt and c-abl–deficient mice. VEGF-saturated or PBS sham Hydron pellets were implanted in corneas of 3-wk-old mice and 7 d postimplantation corneas were examined using slit-lamp biomicroscopy.
Mentions: Because VEGF is involved in the development of hyperoxia-induced retinal vasoproliferation 5 and mice deficient in c-abl failed to develop hyperoxia-induced retinopathy, we sought to determine if mice that lack c-abl could respond normally to VEGF. To examine if homozygous c-abl mice generate an angiogenic response to exogenously supplied VEGF, a corneal angiogenesis assay was employed 35. A PBS sham or VEGF-saturated Hydron pellet was implanted surgically in corneas of 3-wk-old wt and homozygous mice. New blood vessels emerged from the limbal vasculature of wt and c-abl−/− mice toward the VEGF-saturated pellet, whereas no vessels were observed in animals with sham pellets (Fig. 5). The density of angiogenic vessels emerging from the limbus toward the pellet was similar between +/+ and −/− mice. These observations demonstrate that c-abl activity is not required for VEGF-induced signal transduction and that the c-abl−/− mice responded normally to the ectopic administration of VEGF.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

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 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 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.

Show MeSH
Related in: MedlinePlus