Retinopathy of Prematurity: Role of MicroRNA-21 in Pathological Newvascularization

Abstract

Retinopathy of prematurity (ROP) is a disease that occurs in premature infants weighing 1250g or less. ROP causes abnormal blood vessels to grow in the retina. This growth can cause the retina to detach from the back of the eye, leading to blindness in severe cases. ROP affects approximately 14,000 infants, and 90% of those affected have only mild disease. However, 1,100-1,500 children develop disease severe enough to require medical treatment, and 400-600 infants each year in the U.S. become legally blind from ROP. To study the mechanisms of abnormal vascularization in the retina we use a mouse model of oxygen induced retinopathy (OIR), which is a standard experimental model for ROP. In mice the retinal vasculature normally starts to develop around birth and is fully mature around 3 weeks after birth. To trigger OIR, we expose 7-day-old mouse pups to hyperoxia (70% O2), which results in regression of the vasculature. When the animals are returned to room air (21% O2) after five days in oxygen, a neovascular response is triggered. MicroRNAs, short noncoding RNAs that inhibit gene expression through the post-transcriptional repression of their target mRNAs, emerged as key regulators of diverse biologic processes. In this study we will determine the role of miR-21, a specific microRNA that has been involved in pathological angiogenesis, by blocking its activity using in vivo delivery of miR-21 inhibitors (antagomiR) in a mouse model of OIR and in vitro using isolated retinal microvascular cells subjected to hypoxia. The obtained results from western blots and qPCR suggest miR-21 expression is increased and tissue inhibitor of metalloprotease-3 (TIMP3), a target gene of miR-21, expression is decreased in retinal endothelial cells exposed to hypoxia.