Lutein-in-Extra-Virgin-Olive-Oil Supplementation as a Multifaceted Nutritional Intervention for Retinopathy of Prematurity: Evidence from the Mouse Oxygen-Induced Retinopathy Model
4 affiliations
- 1Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, 999077 Hong Kong, China
- 2School of Biological Sciences, The University of Hong Kong, 999077 Hong Kong, China
- 3Department of Ophthalmology, Charité – Universitätsmedizin Berlin, 12203 Berlin, Germany
- 4Department of Ophthalmology, Vancouver General Hospital, University of British Columbia, V5Z 3N9, Vancouver, BC, Canada
Abstract
Background: Retinopathy of prematurity (ROP) is a predominant contributor to preventable childhood blindness driven by oxidative stress and inflammation, but with limited treatment options. Safe, non-invasive adjunctive strategies become attractive. Lutein displays antioxidant and anti-inflammatory properties, but its clinical efficacy remains controversial. We proposed that formulating lutein in extra-virgin olive oil (EVOO) might enhance its absorption and efficacy in ROP. Here, we evaluated the effects of lutein-in-EVOO (LEVOO) in oxygen-induced retinopathy (OIR), a mouse model of ROP. Methods: C57BL/6J mouse neonates received daily gavage of LEVOO (0.4 μg/g, 1.8 μg/g and 3.6 μg/g of lutein in EVOO) after OIR challenge from postnatal day (P) 12 to P16. Assessments were conducted at P17, including retinal vasculature, function, cytoarchitecture, inflammation, and oxidative damage; serum biochemical and antioxidant profiles; and proteomic analysis and targeted retinal metabolomic analysis. Results: Oral supplementation of LEVOO was well-tolerated and safe in mouse neonates. It reduced retinal avascular and neovascular areas, increased electroretinographic b-wave amplitudes, and restored amacrine cells and rod bipolar cells. LEVOO administration reduced oxidative damage and activated microglia. LEVOO administration inhibited the hypoxia-inducible factor-1α (HIF-1α)/macrophage migration inhibitory factor (MIF) signaling and low-density lipoprotein receptor-related protein-1 (LRP1)-dependent cyclophilin A (CypA)/matrix metalloproteinase-9 (MMP9) signaling. It also helped to partially restore retinal docosahexaenoic acid and dopamine in OIR mice. Conclusion: LEVOO demonstrated multifaceted efficacy in OIR. It reconstructed retinal vasculature, restored retinal function, and rescued neuronal cell loss with strong antioxidative and anti-inflammatory effects. Collectively, these findings establish LEVOO as a promising non-invasive complementary strategy for ROP.
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BibTeX
@article{ye2026luteininextravirginoliveoil,
title = {{Lutein-in-Extra-Virgin-Olive-Oil Supplementation as a Multifaceted Nutritional Intervention for Retinopathy of Prematurity: Evidence from the Mouse Oxygen-Induced Retinopathy Model}},
author = {Xiaoyuan Ye and Lu Xiang and Ka Yee Chen and Leo O Lai and Jetty Chung-Yung Lee and Antonia M. Joussen and Wai-Ching Lam and Amy C. Y. Lo},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213616},
url = {https://www.mdpi.com/2072-6643/18/21/3616},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lutein-in-Extra-Virgin-Olive-Oil Supplementation as a Multifaceted Nutritional Intervention for Retinopathy of Prematurity: Evidence from the Mouse Oxygen-Induced Retinopathy Model
AU - Xiaoyuan Ye
AU - Lu Xiang
AU - Ka Yee Chen
AU - Leo O Lai
AU - Jetty Chung-Yung Lee
AU - Antonia M. Joussen
AU - Wai-Ching Lam
AU - Amy C. Y. Lo
PY - 2026
DA - 2026/10/30
JO - Nutrients
DO - 10.3390/nu18213616
UR - https://www.mdpi.com/2072-6643/18/21/3616
AB - Background: Retinopathy of prematurity (ROP) is a predominant contributor to preventable childhood blindness driven by oxidative stress and inflammation, but with limited treatment options. Safe, non-invasive adjunctive strategies become attractive. Lutein displays antioxidant and anti-inflammatory properties, but its clinical efficacy remains controversial. We proposed that formulating lutein in extra-virgin olive oil (EVOO) might enhance its absorption and efficacy in ROP. Here, we evaluated the effects of lutein-in-EVOO (LEVOO) in oxygen-induced retinopathy (OIR), a mouse model of ROP. Methods: C57BL/6J mouse neonates received daily gavage of LEVOO (0.4 μg/g, 1.8 μg/g and 3.6 μg/g of lutein in EVOO) after OIR challenge from postnatal day (P) 12 to P16. Assessments were conducted at P17, including retinal vasculature, function, cytoarchitecture, inflammation, and oxidative damage; serum biochemical and antioxidant profiles; and proteomic analysis and targeted retinal metabolomic analysis. Results: Oral supplementation of LEVOO was well-tolerated and safe in mouse neonates. It reduced retinal avascular and neovascular areas, increased electroretinographic b-wave amplitudes, and restored amacrine cells and rod bipolar cells. LEVOO administration reduced oxidative damage and activated microglia. LEVOO administration inhibited the hypoxia-inducible factor-1α (HIF-1α)/macrophage migration inhibitory factor (MIF) signaling and low-density lipoprotein receptor-related protein-1 (LRP1)-dependent cyclophilin A (CypA)/matrix metalloproteinase-9 (MMP9) signaling. It also helped to partially restore retinal docosahexaenoic acid and dopamine in OIR mice. Conclusion: LEVOO demonstrated multifaceted efficacy in OIR. It reconstructed retinal vasculature, restored retinal function, and rescued neuronal cell loss with strong antioxidative and anti-inflammatory effects. Collectively, these findings establish LEVOO as a promising non-invasive complementary strategy for ROP.
SN - 2072-6643
ER -