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 language | English (US) |
|---|---|
| Pages (from-to) | 1383-1391 |
| Number of pages | 9 |
| Journal | Journal of Experimental Medicine |
| Volume | 193 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 18 2001 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - c-Abl is required for the development of hyperoxia-induced retinopathy
AU - Nunes, Irene
AU - Higgins, Rosemary D.
AU - Zanetta, Lucia
AU - Shamamian, Peter
AU - Goff, Stephen P.
PY - 2001/6/18
Y1 - 2001/6/18
N2 - 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.
AB - 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.
KW - DNA damage
KW - Nonreceptor tyrosine kinase
KW - Oxidative stress
KW - Retinal angiogenesis
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=0035908097&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035908097&partnerID=8YFLogxK
U2 - 10.1084/jem.193.12.1383
DO - 10.1084/jem.193.12.1383
M3 - Article
C2 - 11413193
AN - SCOPUS:0035908097
VL - 193
SP - 1383
EP - 1391
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 12
ER -