> Publications > Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway

Photorefractor

Publication

February 23, 2026 • ✎ STRIA TECH

Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway

Pathway of Lutein action to protect ciliary muscle

Topics:

Aging

Myopia, Refractive Development and Eye Growth

Ocular and CNS Toxicity Models

Systemic Aging and CNS decline

Toxicity

Publication

Phytomedicine (Nov 01, 2024) Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway

Gao N, Gao X, Du M, Xiang Y, Zuo H, Huang R, Wan W, Hu K

DOI: 10.1016/j.phymed.2024.155982 >>

This research explored how lutein, a plant nutrient found in leafy greens, might help the aging muscles in the eye that control focusing (the ciliary muscle). In older guinea pigs, lutein reduced harmful oxidative stress in the ciliary muscle, improved its ability to help the eye change focus, and lowered age-related changes in vision. The protective effect appears to work through a cellular antioxidant system known as the Keap1/Nrf2/ARE pathway, which helps cells defend against damage. In lab-grown muscle cells, lutein also reduced signs of aging and boosted protective proteins, suggesting it could help maintain eye focusing function as people age. Striatech’s Photorefractor measured refractive state and accommodative response, enabling evaluation of lutein’s effects on age-related visual function.

Background: Aging-induced decline in ciliary muscle function is an important factor in visual accommodative deficits in elderly adults. With this study, we provide an innovative investigation of the interaction between ciliary muscle aging and oxidative stress. Methods: Tricolor guinea pigs were used for the experiments in vivo and primary guinea pig ciliary smooth muscle cells were used for the experiments in vitro.Results: We enriched for genes associated with muscle-aging-lutein relationship using bioinformatics, including Nuclear factor-erythroid 2-related factor-2 (Nrf2), Glutathione Peroxidase (GPx) gene family, Superoxide Dismutase (SOD) gene family, NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO-1). After gavage to aged guinea pigs, lutein reduced Reactive Oxygen Species (ROS) and P21 levels in senescent ciliary muscle; lutein decreased refractive error and restored accommodation of the eye. In addition, lutein increased GPx, SOD, and Catalase (CAT) levels in serum; lutein increased GPx and CAT levels in ciliary bodies. Lutein regulated the expression of proteins such as Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and downstream proteins in senescent ciliary bodies. Similarly, guinea pig ciliary muscle cell senescence was associated with oxidative stress. In vitro, 100 μM lutein reversed the damage caused by 800 μM H2O2; it reduced Senescence-Associated β-galactosidase (SA-β-Gal) and ROS activites, cell apoptosis and cell migration. Also, lutein increased the expression of smooth muscle contractile proteins. Lutein also increased the expression of Nrf2, GPx2, NQO1 and HO-1, decreased the expression of Keap1. A reduction in Nrf2 activity led to a reduction in the ability of lutein to activate antioxidant enzymes in the cells, thus reducing its inhibitory effect on cell senescence. Conclusion: lutein improved resistance to oxidative stress in senescent ciliary muscle in vivo and in vitro by regulating the Keap1/Nrf2/Antioxidant Response Element pathway. We have innovatively demonstrated the molecular pharmacological mechanism by which lutein reverse age-related ciliary muscle systolic and diastolic deficits.