Lutein and Zeaxanthin Protect against Light-Induced Retinopathy in a Mouse Model

by | Dec 7, 2020 | 2018, Eye Health, Lutein, Zeaxanthin

Written by Joyce Smith, BS. In a mouse model, lutein, zeaxanthin and mesozeaxanthin (L/Zi) protected retinal photoreceptors against blue light damage by mitigating oxidative stress in the endoplasmic reticulum, thus preventing photoreceptor damage and improving visual impairment.

blue light - eye healthExcessive light exposure often leads to photoreceptor degeneration 1 and when cumulative, can cause age-related macular degeneration (AMD) 2 and ultimately blindness 3. This photoreceptor loss is due to light-induced production of reactive oxygen species (ROS). Endoplasmic reticulum stress (ERS) can lead to retinal degeneration in AMD 4 and has been shown to contribute to retinal diseases such as retinal pigmentosa (RP), diabetic retinopathy 5 and glaucoma 6.

Lutein, zeaxanthin and mesozeaxanthin are xanthophyll carotenoids (a class of oxygen-containing carotenoid pigments) found in fruits and vegetables 7. They make up 80-90% of the carotenoids in the human retina 8 where they function as potent antioxidants and filters of blue light. They play a critical role in preserving visual function, and are especially important today as exposure to blue light from a variety of light sources has dramatically increased. While Science has sufficiently established the protective qualities of these macular carotenoids 9, additional work must be done to identify their protective mechanisms.  This study investigates 10 the protective effects of L/Zi supplementation in a mouse model of early retinal cell degeneration and attempts to identify the underlying mechanisms of oxidative stress and particularly ERS.

Male BALB/cJ mice (9–13 weeks old) were given L/Zi, (10 mg/kg of body weight) or a placebo  daily for 5 days via oral gavage, were then adapted to darkness for 12 hours and finally, after having pupils dilated, were exposed to blue light (5000 lx) for 1 hour. Electroretinography (ERG), TUNEL Analysis (to detect DNA breaks and cell apoptosis), measurement of the thickness of the outer nuclear layer (ONL), and Western blot analysis to identify the presence of proteins and statistical analysis were completed.

L/Zi treatment had a better protective effect on retinal function than the control group as evidenced by significantly greater retinal cellular light damage in the control group than in the L/ZI group (p<0.01)

  • Outer layer retinal (ONL) thickness was significantly less in the control group than that in L/Zi treatment group (p<0.05)
  • L/Zi significantly reduced OS in Light-Damaged Retinas of treatment compared to control group
    • L/Zi significantly downregulated C-Jun N-terminal kinase (JNK)and reduced the ratio of protein densities p-JNK to t-JNK in control versus treatment  groups (p<0.01)
    • L/Zi significantly upregulated Nrf2 in light-damaged retinas of control group versus treatment group, p < 0.05)

With respect to endoplasmic reticulum, L/Zi significantly reduced ERS markers of oxidative stress in the light-damaged retinas of the treatment group compared to the control group.

Researchers believe that blue light exposure upregulates genes which damage retinol photoreceptors by generating oxidative stress. This study shows for the first time that blue light causes damage to retinal tissue by promoting oxidative stress in the endoplasmic reticulum and that administration of lutein and zeaxanthin treatment significantly downregulates the genes involved in promoting ROS. This study also addresses the growing public health issue of blue light exposure and reinforces the need for due diligence in the maintenance of healthy vision through adequate lutein and zeaxanthin intake.

Source: Yu, Minzhong, Weiming Yan, and Craig Beight. “Lutein and zeaxanthin isomers protect against light-induced retinopathy via decreasing oxidative and endoplasmic reticulum stress in BALB/cJ mice.” Nutrients 10, no. 7 (2018): 842.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Posted December 7, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Aziz MK, Ni A, Esserman DA, Chavala SH. Evidence of early ultrastructural photoreceptor abnormalities in light-induced retinal degeneration using spectral domain optical coherence tomography. British Journal of Ophthalmology. 2014;98(7):984-989.
  2. Dong Z, Li J, Leng Y, et al. Cyclic intensive light exposure induces retinal lesions similar to age-related macular degeneration in APPswe/PS1 bigenic mice. BMC neuroscience. 2012;13(1):34.
  3. Cipriani V, Hogg RE, Sofat R, et al. Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related Macular Degeneration. JAMA Ophthalmol. 2017;135(9):909-916.
  4. Libby RT, Gould DB. Endoplasmic reticulum stress as a primary pathogenic mechanism leading to age-related macular degeneration. Adv Exp Med Biol. 2010;664:403-409.
  5. Sánchez-Chávez G, Hernández-Ramírez E, Osorio-Paz I, Hernández-Espinosa C, Salceda R. Potential role of endoplasmic reticulum stress in pathogenesis of diabetic retinopathy. Neurochemical research. 2016;41(5):1098-1106.
  6. Ha Y, Liu H, Xu Z, et al. Endoplasmic reticulum stress-regulated CXCR3 pathway mediates inflammation and neuronal injury in acute glaucoma. Cell Death Dis. 2015;6(10):e1900.
  7. Eisenhauer B, Natoli S, Liew G, Flood VM. Lutein and Zeaxanthin-Food Sources, Bioavailability  and Dietary Variety in Age-Related Macular  Degeneration Protection. Nutrients. 2017;9(2).
  8. Vishwanathan R, Schalch W, Johnson EJ. Macular pigment carotenoids in the retina and occipital cortex are related in humans. Nutritional neuroscience. 2016;19(3):95-101.
  9. Mares, J. Lutein and Zeaxanthin Isomers in Eye Health and Disease. Annu. Rev. Nutr. 2016, 36, 571–602.[CrossRef] [PubMed]
  10. Yu, Minzhong, Weiming Yan, and Craig Beight. “Lutein and zeaxanthin isomers protect against light-induced retinopathy via decreasing oxidative and endoplasmic reticulum stress in BALB/cJ mice.” Nutrients 10, no. 7 (2018): 842.