Retinopathy of prematurity: Metabolic risk factors

Abstract

At preterm birth, the retina is incompletely vascularized. Retinopathy of prematurity (ROP) is initiated by the postnatal suppression of physiological retinal vascular development that would normally occur in utero. As the neural retina slowly matures, increasing metabolic demand including in the peripheral avascular retina, leads to signals for compensatory but pathological neovascularization. Currently, only late neovascular ROP is treated. ROP could be prevented by promoting normal vascular growth. Early perinatal metabolic dysregulation is a strong but understudied risk factor for ROP and other long-term sequelae of preterm birth. We will discuss the metabolic and oxygen needs of retina, current treatments, and potential interventions to promote normal vessel growth including control of postnatal hyperglycemia, dyslipidemia and hyperoxia-induced retinal metabolic alterations. Early supplementation of missing nutrients and growth factors and control of supplemental oxygen promotes physiological retinal development. We will discuss the current knowledge gap in retinal metabolism after preterm birth.

A Prospective Analysis of the Retinopathy of Prematurity Correlated with the Inflammatory Status of the Extremely Premature and Very Premature Neonates

“…Regarding the inflammatory markers selected for this study, IL-6 was chosen for its well-established role as a primary pro-inflammatory cytokine and its recognized association with neonatal complications, such as sepsis, necrotizing enterocolitis, and even ROP [ 9 , 51 ]. Similarly, CRP, an acute-phase reactant that rises rapidly during inflammation and infection, was selected for its routine use in monitoring these conditions and its proposed relationship with ROP development [ 17 , 51 ]. The combined assessment of these two markers allows for a more comprehensive understanding of the neonates’ inflammatory status.…”

“…Extremely premature and very premature neonates are known to be at a higher risk of developing ROP due to their underdeveloped retinal vasculature and their increased susceptibility to oxidative stress and inflammation [ 14 ]. In these infants, the immature immune system and exposure to various stressors, such as infections and mechanical ventilation, can result in a heightened inflammatory response, further contributing to the development and progression of ROP [ 15 , 16 , 17 ].…”

Emerging role of metabolic reprogramming in hyperoxia-associated neonatal diseases

“…This condition is often complicated by oxygen therapy for respiratory diseases [ 77 ]. Recent studies have identified metabolic abnormalities in the occurrence and progression of ROP [ 78 ]. Despite the existence of many mitochondria, photoreceptors, which are a crucial component of the outer retina, primarily rely on aerobic glycolysis rather than OXPHOS for metabolism.…”

FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP

“…Mechanisms behind delayed physiological retinal vascularization are not fully understood. It is well established that hyperoxia causes suppression of physiological retinal vascular growth [ 5 ]. However, there is another very important factor contributing to suppression of physiological retinal vascular growth.…”