1. From: Through The Eyes of a Child: Understanding Retinopathy through ROP The Friedenwald Lecture
Invest. Ophthalmol. Vis. Sci ;49(12): doi: /iovs
Figure Legend:
Schematic representation of IGF-I, VEGF, Epo, and ω-3 PUFA control of blood vessel development in ROP. (A) In utero, VEGF is found at the growing front of vessels. IGF-I is sufficient to allow vessel growth, Epo is normal, and ω-3 PUFAs are provided by the mother. (B) With premature birth and loss of the placenta, IGF-I and ω-3 PUFA levels fall, and the relative hyperoxia of the extrauterine environment suppress VEGF and Epo. Vascular growth ceases. Both endothelial cell survival (Akt) and proliferation (mitogen-activated protein kinase) pathways are compromised. With low IGF-I and cessation of vessel growth, a demarcation line forms at the vascular front. Supplemental oxygen in some premature infants may further suppress VEGF and Epo, increasing inhibition of vessel growth. (C) As the premature infant matures, the developing but nonvascularized retina becomes hypoxic. VEGF and Epo increase in retina and vitreous. With maturation, the IGF-I level slowly increases. Without an external source, ω-3 PUFA levels will remain low. When the IGF-I level reaches a threshold at ∼34 weeks gestation, with high VEGF and Epo levels in the vitreous, endothelial cell survival and proliferation driven by VEGF may proceed. Neovascularization ensues at the demarcation line, growing into the vitreous. (D) There are two ways to prevent the neovascular proliferation: (1) Inhibition of the neovascular phase. If elevated VEGF and Epo vitreal levels are suppressed and IGF-1 is normalized and ω-3 PUFA is provided, normal retinal vessel growth can proceed. (2) Inhibition of the vessel loss phase. If IGF-1, Epo, and VEGF levels are increased to normal in utero levels in phase I, then vessel loss is suppressed, and the neovascular phase II will not occur. With normal vascular growth and blood flow, oxygen suppresses VEGF expression, and so it will no longer be overproduced.
Date of download: 10/16/2017
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