Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4/Bco2 double knockout mice

Arunkumar, Ranganathan; Gorusupudi, Aruna; Li, Binxing; Blount, J. David; Nwagbo, Uzoamaka; Kim, Hye Jin; Sparrow, Janet R.; Bernstein, Paul S.

doi:10.1016/j.exer.2021.108680

Cited by 25 publications

(22 citation statements)

References 61 publications

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“…Here, RPE cells supplemented with bovine retinal extract showed much more 488-nm autofluorescent material in STGD1 versus control cells. In vivo , the bisretinoid chemical structure renders them susceptible to further modification and fragmentation, thereby generating reactive species responsible for increased oxidative stress and destabilization of cellular physiological activities [ 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Similar to STGD1 donor eyes [ 13 ], 12-month-old STGD1 RPE cells showed markedly increased levels of the lipid peroxidation marker, 4-HNE.…”

Section: Discussionmentioning

confidence: 99%

Membrane Attack Complex Mediates Retinal Pigment Epithelium Cell Death in Stargardt Macular Degeneration

Kady

et al. 2022

Cells

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Recessive Stargardt disease (STGD1) is an inherited retinopathy caused by mutations in the ABCA4 gene. The ABCA4 protein is a phospholipid-retinoid flippase in the outer segments of photoreceptors and the internal membranes of retinal pigment epithelial (RPE) cells. Here, we show that RPE cells derived via induced pluripotent stem-cell from a molecularly and clinically diagnosed STGD1 patient exhibited reduced ABCA4 protein and diminished activity compared to a normal subject. Consequently, STGD1 RPE cells accumulated intracellular autofluorescence-lipofuscin and displayed increased complement C3 activity. The level of C3 inversely correlated with the level of CD46, an early negative regulator of the complement cascade. Persistent complement dysregulation led to deposition of the membrane attack complex on the surface of RPE cells, decrease in transepithelial resistance, and subsequent cell death. These findings are strong evidence of complement-mediated RPE cell damage in STGD1, in the absence of photoreceptors, caused by reduced CD46 regulatory protein.

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Section: Discussionmentioning

confidence: 99%

Membrane Attack Complex Mediates Retinal Pigment Epithelium Cell Death in Stargardt Macular Degeneration

Kady

et al. 2022

Cells

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“… 12 Arunkumar and colleagues also recently demonstrated reduced bisretinoid formation following lutein and zeaxanthin supplementation in a mouse model of SD. 13 …”

Section: Discussionmentioning

confidence: 99%

Late-onset Stargardt disease

Alsberge

2022

American Journal of Ophthalmology Case Reports

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“…Carotenoid supplementation, which provides a source of retinoids, has been suggested as a potential nutritional approach to improving STGD outcomes by protecting the macula ( 221 ), due to observed lower carotenoid serum levels in STGD patients compared to controls ( 234 ). While carotenoid supplementation has a positive effect on visual performance in ABCA4-knockabout mice ( 235 ), no nutritional trials have been conducted as of yet ( 219 ). Although there is conflicting evidence regarding dietary vitamin A and STGD outcomes ( 225 , 226 ), laboratory evidence of vitamin A supplementation driving greater lipofuscin accumulation ( 161 ), albeit without significant effects on retinal function ( 57 , 224 ) has led to recommendations for STGD patients to avoid retinoid supplements ( 221 ).…”

Section: Clinical Applications and Directions For Researchmentioning

confidence: 99%

Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease

2022

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The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt’s disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt’s or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A’s functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis.

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Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4/Bco2 double knockout mice

Cited by 25 publications

References 61 publications

Membrane Attack Complex Mediates Retinal Pigment Epithelium Cell Death in Stargardt Macular Degeneration

Membrane Attack Complex Mediates Retinal Pigment Epithelium Cell Death in Stargardt Macular Degeneration

Late-onset Stargardt disease

Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease

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