ArticleProceedings of the National Academy of Sciences of the United States of America2014
ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy-Beyond Classical Gene Candidates.Frontiers in genetics · 2022Pooled it
- Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.American journal of ophthalmology · 2022Trial
- Visual cycle-derived bisretinoids as endogenous natural products: enzyme-free formation, photochemical reactivity, and retinal degeneration.Natural product reports · 2026Review
- Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids.Stem cells (Dayton, Ohio) · 2026Article
- ABCA4-Associated Retinal Degeneration in 8 Families From the Three Provinces of Northeast China: Identification and Characterization of Potentially Novel Variants.Molecular genetics & genomic medicine · 2026Article
- Using RNA-targeting CRISPR-Cas13 and engineered U1 systems to targetMolecular therapy. Nucleic acids · 2026Article
- More insights from Abca4The Journal of biological chemistry · 2026Article
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Rationally Designed, Short-Acting RPE65 Inhibitors for Visual Cycle-Associated Retinopathies.Journal of medicinal chemistry · 2025Article
- Stargardt's Disease: Molecular Pathogenesis and Current Therapeutic Landscape.International journal of molecular sciences · 2025Review
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Deciphering the impact of ABCA4 genetic variants of unknown significance in inherited retinal disease through computational and functional approaches.Advances in protein chemistry and structural biology · 2025Review
- Bisretinoids as a Source of Early Photoreceptor Pathology in Stargardt Disease.Ophthalmic research · 2025Review
- Vitamin A supply in the eye and establishment of the visual cycle.Current topics in developmental biology · 2025Review
- Abca4, mutated in Stargardt disease, is required for structural integrity of cone outer segments.Disease models & mechanisms · 2025Article
- Sphingolipid Levels and Processing of the Retinyl Chromophore in the Retina of a Mouse Model of Niemann-Pick Disease.Investigative ophthalmology & visual science · 2024Article
- Therapeutic Extracellular Vesicles from Tonsil-Derived Mesenchymal Stem Cells for the Treatment of Retinal Degenerative Disease.Tissue engineering and regenerative medicine · 2023Article
- ABCA4 Variant c.5714+5G>A in Trans With Null Alleles Results in Primary RPE Damage.Investigative ophthalmology & visual science · 2023Article
- A Splicing Variant in RDH8 Is Associated with Autosomal Recessive Stargardt Macular Dystrophy.Genes · 2023Article
- Primary versus Secondary Elevations in Fundus Autofluorescence.International journal of molecular sciences · 2023Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-trans-retinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.