The role of reactive oxygen species and oxidative signaling in retinopathy of prematurity

Oxidative stress has been proposed to play a role in the pathogenesis of retinopathy of prematurity (ROP) for years, because of the effects of changing oxygen concentrations that occur in the preterm infant on reactive oxygen species (ROS) generation, the reduced antioxidant reserve in the preterm infant, and the high concentration of polyunsaturated fatty acids in the retina. In addition, greater evidence exists that oxidative compounds are involved in triggering angiogenesis and apoptosis, two events that have relevance to the development of features of severe ROP, namely, aberrant neovascularization into the vitreous and avascular retina. However, oxidative compounds are important as transcription factors for pathways involved in vascular development and as a first line of defense against invading microorganisms. Clinical studies designed to test the effect of antioxidants on the development of ROP have not yielded clear-cut results or have been associated with toxicity to the overall health of the preterm infant. In this chapter, we will review the role of ROS in the developing preterm infant and examine evidence from clinical studies and laboratory models.