Retinopathy of prematurity (ROP) is a blinding disease of premature infants resulting from development of abnormal blood vessels in the immature retina. It has been well established that excess oxygen is an important causative factor in the pathogenesis of ROP. Nevertheless, despite the more careful use of oxygen, the incidence of ROP is increasing in the United States. In addition, current treatments for severe ROP fail to prevent blindness in a large proportion of infants. Therefore, further research into the pathogenesis of ROP is critical to increase our understanding of the disease and to develop new methods of prevention and treatment. Infants who never experience hyperoxia (e.g., those with congenital heart disease) may also develop ROP. For these infants in particular, and for premature neonates in general, systemic acidosis has been implicated as a risk factor in the development of ROP. A new neonatal animal model has been developed that allows study of metabolic acidosis and retinal neovascularization. The investigator has confirmed that metabolic acidosis alone leads to preretinal neovascularization in the retina of immature animals, and has termed this model """"""""metabolic acidosis-induced retinopathy"""""""" (MAIR). Using this model, the investigator proposes to characterize the effect of acidosis on the immature retina and investigate biochemical and molecular mechanisms. These studies may lead to new avenues of prevention and treatment of ROP. The primary hypothesis for this series of experiments is that: """"""""acidosis is a risk factor for ROP in human neonates."""""""" This leads to the following secondary hypotheses that will be tested in the MAIR model, which is that: (1) a dose-response relationship exists between the extent of metabolic acidosis and the severity of retinopathy in the neonatal rat model; (2) neovascularization in the acidotic model is mediated by down-regulation followed by up-regulation of one or more growth factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF-1); and (3) the retinopathy can be prevented by reversal of acidosis.
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