Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity

Abstract

Background Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischemia contributes to its pathogenesis and lutein protects against ischemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. Methods Mouse pups were exposed to 75% oxygen for five days and returned to room air for another five days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. Results Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. Conclusions Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity due to its role in facilitating the revascularization of normal vasculature.

Ursodeoxycholic Acid Halts Pathological Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy

“…These effects were confirmed when UDCA was administered only during the hypoxic phase (P12-P17), but not the hyperoxic stage (P7-P12), thus revealing the anti-angiogenic properties of this compound on the ischemic retinal vasculature. Concomitant with these findings, we also found that UDCA prevented reactive gliosis, loss of neuronal cells, and breakdown of the BRB, which are all key features of OIR and ROP [31,[41][42][43]. To confirm the anti-angiogenic ability of UDCA, we also determined that this BA decreases VEGF expression in the OIR retinas and prevents VEGF pro-angiogenic and pro-permeability effects in HuREC in vitro.…”

“…Reactive gliosis and loss of retinal ganglion cells are features associated with OIR in mice [ 31 ]. In agreement with previous reports, we observed significant reactive gliosis in OIR mice, as indicated by increased GFAP immunoreactivity stretching through the entire retina ( Figure 5 A).…”

Early Enteral Administration of a Complex Lipid Emulsion Supplement Prevents Postnatal Deficits in Docosahexaenoic and Arachidonic Acids and Increases Tissue Accretion of Lipophilic Nutrients in Preterm Piglets

“…Similar to many other nutrients, preterm delivery results in a lack of body fat and thus low body stores of these lipophilic molecules with subsequent decline due to inadequate replacement . The recommended requirements and levels of deficiency of most of these micronutrients, with the exception of vitamin D 3 , are unknown; however, their importance in eye, brain, bone, and immune development and their role as antioxidants have been postulated in infant development . The concentrated, highly emulsified lipid supplement provided in this study resulted in adequate absorption of these important lipophilic nutrients.…”

Lutein Supplementation for Eye Diseases

“…Using the murine OIR model, lutein treatment was shown to promote normal retinal revascularization during the hypoxic stage by promoting endothelial tip cell formation and maintaining astrocytic template [ 136 ]. Nevertheless, the study was unable to demonstrate lutein’s effects in reducing retinal vasculature loss in initial hyperoxic phase, which is probably contributed by the insufficient intake of nutrients and maternal growth factors in the preterm infants.…”