June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4-/-/Bco2-/- double KO Mice
Author Affiliations & Notes
  • Arunkumar Ranganathan
    Moran eye center, University of Utah Health, Salt Lake City, Utah, United States
  • Aruna Gorusupudi
    Moran eye center, University of Utah Health, Salt Lake City, Utah, United States
  • Binxing Li
    Moran eye center, University of Utah Health, Salt Lake City, Utah, United States
  • David Blount
    Moran eye center, University of Utah Health, Salt Lake City, Utah, United States
  • Fu-Yen Chang
    Moran eye center, University of Utah Health, Salt Lake City, Utah, United States
  • Janet R. Sparrow
    Department of Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States
  • Paul S Bernstein
    Moran eye center, University of Utah Health, 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; Janet Sparrow, None; Paul Bernstein, None
  • Footnotes
    Support  R01EY011600, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2974. doi:
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      Arunkumar Ranganathan, Aruna Gorusupudi, Binxing Li, David Blount, Fu-Yen Chang, Janet R. Sparrow, Paul S Bernstein; Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4-/-/Bco2-/- double KO Mice. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2974.

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

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Abstract

Purpose : In autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD), excessive accumulation of lipofuscin is associated with retinal pigment epithelium (RPE) cell death, photoreceptor cell damage, and vision loss. A2E and iso-A2E are prominent fluorophores of ocular lipofuscin that mediate phototoxicity and degeneration. Previous work from our lab in vitro, in quail eyes, and in human donor eyes have indicated that macular carotenoids (MC) can attenuate bisretinoid formation and phototoxicity, but mouse studies have been hampered by poor carotenoid uptake due to their very active carotenoid cleavage enzyme, Bco2. In this study, we have crossed Bco2 KO “macular pigment mice” with a mouse model of STGD1.

Methods : Abca4-/-/Bco2-/- and Abca4-/- mice on C57BL6/J background were fed with lutein, zeaxanthin, or a placebo chow (∼2.6 mg of carotenoid/mouse/day; DSM, Kaiseraugst, Switzerland; n=12/group) for 3 months, and their optokinetic response (OKR), electroretinography (ERG) and optical coherence tomography (OCT) were measured after 1-3 months of carotenoid supplementation. Mice were sacrificed after 3 months of supplementation, and their blood and tissues (eye, liver, and brain) were collected. A2E and iso-A2E levels from RPE/choroid and carotenoid levels from the retina were quantified by HPLC

Results : Lutein and zeaxanthin supplemented Abca4-/-/Bco2-/- mice had 33-71% lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow (p<0.05) and had improved visual performance. Carotenoid supplementation in Abca4-/- mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual acuity compared to the control diet-fed group. There was a statistically significant inverse correlation between MC levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Scotopic and photopic a and b-wave response and photoreceptor cell viability did not show any significant differences relative to WT mice of same age in either mouse line, irrespective of their supplementation status.

Conclusions : Supplementation with MC effectively reduces bisretinoid formation and improves visual acuity in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.

This is a 2021 ARVO Annual Meeting abstract.

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