endothelin-1 and Retinopathy-of-Prematurity

In addition to its hematopoietic effects, erythropoietin causes an increased release of endothelin-1 and the stimulation of angiogenesis and thereby it may have possible role in development of retinopathy of prematurity (ROP). Our objective was to determine if an association exists between recombinant human erythropoietin (rhEPO) treatment and the development of ROP. Our case-control study involved 85 very low birthweight infants with birthweights <1500 g born during 2003 and 2004. All the infants were divided into two groups on the basis of whether they got rhEPO or not. The rhEPO was given at the dose of 200 to 250 units/kg/dose three times a week for 10 doses. Further duration of rhEPO therapy was decided on the basis of the clinical response. Ophthalmological examinations were done at the age of 5 to 6 weeks and were repeated 1 to 4 weeks after the first examination according to the severity of the ROP disease during their in-hospital stay. Of 85 infants, 56 (66%) received rhEPO and 29 (34%) did not. In the rhEPO-treated group, 12 infants (21%) had ROP; in the non-rhEPO group, 11 infants (38%) developed ROP. This difference is not statistically significant (odds ratio = 2.63; P = 0.10). There was no correlation between the use of rhEPO and the stage of ROP (random sample = -0.01; P = 0.89). There was no significant difference in the incidence of plus, prethreshold, or threshold disease and the treatment required for ROP between the rhEPO-treated and the nontreated group. The study showed there is no significant difference in the incidence and severity of ROP between the rhEPO-treated and nontreated group.

Topics: Case-Control Studies; Endothelin-1; Erythropoietin; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Neovascularization, Physiologic; Recombinant Proteins; Retinopathy of Prematurity; Severity of Illness Index

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.

Topics: Animals; Animals, Newborn; Endothelial Growth Factors; Endothelin-1; Humans; Hyperoxia; Infant, Newborn; Lymphokines; Mice; Mice, Knockout; Neovascularization, Pathologic; Proto-Oncogene Proteins c-abl; Retina; Retinal Vessels; Retinopathy of Prematurity; RNA, Messenger; Transcriptional Activation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors