Lois Smith, MD, PhD
Associate Professor of Ophthalmology
Harvard Medical School/Children’s Hospital
Department of Ophthalmology

MRRC Project(s)

R01 EY08670-08
Retinopathy of Prematurity - Therapies and Mechanism

Retinopathy of prematurity (ROP) is a blinding disease of premature infants. Current ablative treatment destroys retina and is only partially effective in preventing end-stage disease. A medical treatment is essential. ROP occurs in two phases: first, retinal vaso-obliteration occurs with hyperoxia; second, neovascularization (NV) occurs with hypoxia of the avascular retina. In a mouse model of ROP, up-regulation of vascular endothelial growth factor (VEGF) is important in vaso-proliferation and down-regulation of VEGF is important in vaso-obliteration. Inhibition of VEGF inhibits retinal NV. However, total systemic inhibition of VEGF may cause exacerbation of the first phase of ROP and might also pose problems with fetal development. Therefore alternative pathways that control ROP will be important. The overall goal of this proposal is to investigate the therapeutic potential of manipulation of VEGF and IGF-I and the potential of combination therapy to decrease untoward effects of maximum inhibition of each pathway alone. We also intend to further examine the mechanism of IGF-I and VEGF control of both the vaso-obliterative phase and vaso-proliferative phase of ROP and to refine therapy based on this understanding.