Date of Award

Spring 2014

First Advisor

Dr. Yuh-Cherng Chai

Abstract

Retinopathy of prematurity (ROP), a retinal disease characterized by neovascularization and vasoobliteration, is becoming more prevalent in premature infants as technological advances succeed in better sustaining the life of infants that are the result of premature birth. Dimethyloxalylglycine (DMOG) has been proven to lessen the severity of the symptoms of ROP in mice through the inhibition of prolyl hydroxylase, an enzyme crucial to the degradation of hypoxia inducible growth factor (HIF). The identification of DMOG as a potential novel therapeutic treatment for ROP has brought the mechanism by which DMOG functions into question. To further define this mechanism, wild-type (WT) and liver HIF1α knockout mice (LHKO) were injected with DMOG and the subsequent expression of target genes in the liver, kidney, and retina were measured at varying time points. Notable results include the up regulation of erythropoietin (EPO) and angiopoietin-like 3 (ANGPTL3). Such upregulation proves that EPO and ANGPTL3 should be considered a key target in future efforts to prevent the formation of ROP. Furthermore, these results suggest that EPO and ANGPTL3 play a role in protecting the retina from damaging hyperoxic conditions. It is unclear, however, how EPO and ANGPTL3 directly affect the retina, making it worthy of being studied further. This work serves as a solid foundation for future examination of the biochemical mechanism of DMOG in the treatment of ROP.

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