June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Zeaxanthin Effectively Reduces A2E and iso-A2E formation in the Retinal Pigment Epithelium of ABCA4(-/-) /BCO2(-/-) Double KO Mice
Author Affiliations & Notes
  • Arunkumar Ranganathan
    Moran Eye center University of Utah School of Medi, Salt Lake City, Utah, United States
  • Aruna Gorusupudi
    Moran Eye center University of Utah School of Medi, Salt Lake City, Utah, United States
  • Binxing Li
    Moran Eye center University of Utah School of Medi, Salt Lake City, Utah, United States
  • David Blount
    Moran Eye center University of Utah School of Medi, Salt Lake City, Utah, United States
  • Fu-Yen Chang
    Moran Eye center University of Utah School of Medi, Salt Lake City, Utah, United States
  • Paul S Bernstein
    Moran Eye center University of Utah School of Medi, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Arunkumar Ranganathan, None; Aruna Gorusupudi, None; Binxing Li, None; David Blount, None; Fu-Yen Chang, None; Paul Bernstein, None
  • Footnotes
    Support  R01EY011600, Research to prevent blindness
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1509. doi:
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      Arunkumar Ranganathan, Aruna Gorusupudi, Binxing Li, David Blount, Fu-Yen Chang, Paul S Bernstein; Zeaxanthin Effectively Reduces A2E and iso-A2E formation in the Retinal Pigment Epithelium of ABCA4(-/-) /BCO2(-/-) Double KO Mice. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1509.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : A2E and its isomer iso-A2E, major fluorophores of lipofuscin in human retinal pigment epithelium (RPE), are believed to mediate blue light-induced oxidative damage associated with aging and pathogenesis of age-related macular degeneration (AMD). We have hypothesized that increasing dietary intake of the macular pigments (MP) carotenoids lutein and zeaxanthin in individuals at risk of AMD can inhibit formation of A2E and its metabolites and can potentially ameliorate macular degenerative diseases. In order to study the beneficial effect of MP in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (ABCA4)(-/-) /β, β-carotene-9', 10’-oxygenase 2 (BCO2) (-/-) double knockout (KO) mice because ABCA4 KO mice can accumulate A2E and iso-A2E in their RPE, and BCO2 KO mice ("macular pigment mice") can accumulate MP carotenoids in their retinas in a manner similar to humans.

Methods : ABCA4(-/-) /BCO2(-/-) double KO mice and ABCA4(-/-) KO mice on a C57BL6/J background were sub-divided into three groups. Each subgroup was fed with lutein chow, zeaxanthin chow or placebo chow (∼2.6 mg per mouse per day; DSM, Kaiseraugst, Switzerland; n=6 per subgroup) for three months. Mice were sacrificed, and eyes, liver, brain, and blood were collected. RPE A2E and iso-A2E levels and retinal MP levels were measured by HPLC.

Results : A2E, iso-A2E and MP levels of ABCA4(-/-) /BCO2(-/-) double KO mice and ABCA4(-/-) KO mice fed with lutein chow, zeaxanthin chow and placebo chow are shown in Table 1. While lutein and zeaxanthin consistently lowered A2E and iso-A2E levels in all subgroups relative to placebo chow, zeaxanthin's effect was always strongest and was statistically significant only in the double KO mice. In general, A2E and iso-A2E levels were inversely proportional to MP levels.

Conclusions : Supplementation with zeaxanthin effectively inhibits A2E and iso-A2E formation in a double KO mouse model of Stargardt disease designed to accumulate human-like levels of carotenoids. This new Stargardt disease and macular pigment double KO mouse model can be used to further study the effect of nutraceuticals to ameliorate retinal degenerative diseases.

This is a 2020 ARVO Annual Meeting abstract.

 

A2E, iso-A2E, and MP carotenoid levels in ABCA4/BCO Double KO and ABCA4 KO mice fed lutein, zeaxanthin, or placebo chow.

A2E, iso-A2E, and MP carotenoid levels in ABCA4/BCO Double KO and ABCA4 KO mice fed lutein, zeaxanthin, or placebo chow.

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