Premium
Lutein Protects the Retinal Pigment Epithelium Against Hypoxic and Oxidative Stress: In Vitro Studies
Author(s) -
Allison Geoffrey,
Draper Christian,
Soekamto Christa,
Gong Xiaoming,
Rubin Lewis P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.913.3
Subject(s) - lutein , zeaxanthin , xanthophyll , oxidative stress , retinal pigment epithelium , astaxanthin , retinal , chemistry , carotenoid , reactive oxygen species , viability assay , apoptosis , biochemistry , microbiology and biotechnology , biology
Background Oxidative stress‐induced damage to the retinal pigment epithelium (RPE) occurs as part of the pathogenesis of age‐related macular degeneration (AMD) and neovascular retinopathies ( e.g. , retinopathy of prematurity [ROP] and diabetic retinopathy [DR]). The xanthophylls lutein and zeaxanthin are selectively taken up by the RPE, preferentially accumulated in the human macula, and transferred to photoreceptors. The retinal/macular xanthophylls are presumed to protect retinal integrity via their antioxidant, antiactinic, and photoprotective activities. We have investigated effects of various carotenoids (beta‐carotene, lycopene, astaxanthin, lutein, zeaxanthin) on RPE cells subjected to hypoxia or oxidative stress in order to determine effect specificity for the retinal xanthophylls. Methods Human RPE‐derived ARPE‐19 and hTERT‐1 cells were exposed to graded concentrations of specific carotenoids, then subjected to oxidative stress using hydrogen peroxide (H 2 O 2 ) or tert‐ butyl hydroperoxide (tBHP). Hypoxia chambers were used for graded hypoxia to 2% FiO 2 . Carotenoid effects on RPE cell proliferation, viability, apoptosis, and reactive oxygen species (ROS) production were determined by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5 diphenyl tetrazolium bromide (MTT) assays; 2′,7′‐dichloro‐dihydrofluorescein diacetate (H2DCFDA) fluorescence; and flow cytometry. Results Lutein, zeaxanthin, and lycopene, but not beta‐carotene or astaxanthin, decreased RPE cell proliferation under normoxic and hypoxic conditions. Pre‐treating ARPE‐19 cells with lutein, but not with other carotenoids, tielded modest protection from H 2 O 2 ‐ or tBHP‐induced cell loss. However, cell co‐exposure to lutein and tBHP significantly decreased intracellular ROS production and essentially neutralized tBHP‐dependent cell death at tBHP concentrations up to 500 μM (see Figure). Conclusion Lutein inhibits proliferation (and promotes differentiation) of human RPE cells. In this in vitro model, lutein significantly protects the RPE from oxidative stress. These findings contribute to the understanding of protective mechanisms attributable to retinal xanthophylls in eye health and retinopathies. Support or Funding Information Partially funded by TTUHSC El Paso Seed Grants (LPR, XG) and Scholarly Activity & Research Program student awards (GA, CD).