| First Author | Duan LJ | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 4 | Pages | 1881-90 |
| PubMed ID | 21435465 | Mgi Jnum | J:169844 |
| Mgi Id | MGI:4943347 | Doi | 10.1016/j.ajpath.2010.12.016 |
| Citation | Duan LJ, et al. (2011) Prolyl Hydroxylase Domain Protein 2 (PHD2) Mediates Oxygen-Induced Retinopathy in Neonatal Mice. Am J Pathol 178(4):1881-90 |
| abstractText | Retinopathy of prematurity is a major side effect of oxygen therapy for preterm infants, and is a leading cause of blindness in children. To date, it remains unclear whether the initial microvascular obliteration is triggered by degradation of hypoxia inducible factor (HIF) alpha proteins or by other mechanisms such as oxidative stress. Here we show that prolyl hydroxylase domain protein 2 (PHD2), an enzyme mostly responsible for oxygen-induced degradation of HIF-alpha proteins, plays a major role in oxygen-induced retinopathy in mice. In neonatal mice expressing normal amounts of PHD2, exposure to 75% oxygen caused significant degradation of retinal HIF-alpha proteins, accompanied by massive losses of retinal microvessels. PHD2 deficiency significantly stabilized HIF-1alpha, and to some extent HIF-2alpha, in neonatal retinal tissues, and protected retinal microvessels from oxygen-induced obliteration. After hyperoxia-treated neonatal mice were returned to ambient room air, retinal vasculature in PHD2-deficient mice remained mostly intact and showed very little neoangiogenesis. These findings demonstrate a close association between PHD2-dependent HIF-alpha degradation and oxygen-induced retinal microvascular obliteration, and imply that PHD2 may be a promising therapeutic target to prevent oxygen-induced retinopathy. |
