Oral Supplementation of Lutein-in-extra-virgin-olive-oil Improved Retinal Function in Oxygen-Induced Retinopathy Mouse Model

Abstract

<p><strong>Purpose </strong>: Retinopathy of prematurity (ROP) is a major cause of childhood blindness in preterm infants, attributed to oxidative stress. Lutein is a strong antioxidant with the potential to mitigate ROP. To enhance the bioavailability of lutein, extra virgin olive oil (EVOO) was used to dissolve lutein. Here, we explored the potential of oral supplementation of lutein-in-extra-virgin-olive-oil (LEVOO) as a non-invasive management for ROP using a mouse oxygen-induced retinopathy (OIR) model.</p><p><strong>Methods </strong>: Neonatal C57BL/6J mice were exposed to 75% O₂ from postanal day 7 (P7) to P12 followed by daily gavage of different volumes of water, olive oil (OO, for caloric control), or EVOO. Dosing volume was optimized by evaluation of retinal function and pathologic vasculature using electroretinography (ERG) and isolectin-stained retinal flat mounts, respectively on P17. Lutein was then dissolved in 4 mL/kg EVOO (best dosing volume) to attain the intended dosages of 0.4, 1.8, and 3.6 mg/kg (LEVOO). P12 mice after OIR received various dosages of LEVOO via oral gavage daily. On P17, retinal function was assessed with scotopic ERG. Data were analyzed with One-way ANOVA followed by Dunnett’s<em> </em>post hoc test.</p><p><strong>Results </strong>: Mice subjected to OO or EVOO peroral administration displayed similar body weight and a- or b-wave amplitudes in ERG as well as comparable avascular and neovascular areas when compared with water-treated mice. After OIR, LEVOO-treated mice yielded a dose-responsive b-wave amplitude increase measured at various light intensities (0.01, 0.1, 1 and 3 cd.s/m²). Notably, mice treated with LEVOO at 3.6 mg/kg displayed significantly larger b-wave amplitudes (at 1 cd.s/m²) than those treated with EVOO (EVOO: 193.8 ± 20.4 μV, LEVOO 3.6 mg/kg: 304.8 ± 33.9 μV, n=3-6, <em>p</em><0.05).</p><p><strong>Conclusions </strong>: EVOO is a safe oral drug delivery vehicle in the OIR model. LEVOO-treated neonates exhibited improved retinal function, suggesting that LEVOO might rescue bipolar cells after OIR.<br></p>