ArticleInvestigative ophthalmology & visual science2013
A1120, a nonretinoid RBP4 antagonist, inhibits formation of cytotoxic bisretinoids in the animal model of enhanced retinal lipofuscinogenesis.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Visual cycle modulators versus placebo or observation for the prevention and treatment of geographic atrophy due to age-related macular degeneration.The Cochrane database of systematic reviews · 2020Pooled it
- Intracellular Retinoid-Binding Proteins (CRBP, CRALBP, CRABP) as Emerging Drug Targets in Retinal Disease.International journal of molecular sciences · 2026Review
- The Liver-Eye Axis of Dietary Vitamin A Homeostasis: A Review of Mechanisms, Receptors, and Visual Outcomes.Nutrients · 2026Review
- Retinol-binding protein 4 in cardiovascular diseases: mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2026Review
- Targeting Angiogenesis and Visual Cycle in Age-Related Macular Degeneration: The Role of Stem Cells and Vinpocetine.Cureus · 2025Article
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- The Potential Role of Retinol-Binding Protein 4 in Heart Failure: A Review.Reviews in cardiovascular medicine · 2025Review
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway.Journal of cachexia, sarcopenia and muscle · 2024Article
- Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting.EMBO reports · 2024Article
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
- Discovery of Nonretinoid Inhibitors of CRBP1: Structural and Dynamic Insights for Ligand-Binding Mechanisms.ACS chemical biology · 2023Article
- Updates on Emerging Interventions for Autosomal RecessiveJournal of clinical medicine · 2023Review
- Electroretinography as a Biomarker to Monitor the Progression of Stargardt Disease.International journal of molecular sciences · 2022Article
- Review
- Recent Advances in Age-Related Macular Degeneration Therapies.Molecules (Basel, Switzerland) · 2022Review
- Vitamin A aldehyde-taurine adducts function in photoreceptor cells.Redox biology · 2022Article
- Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease.Nutrients · 2022Review
- The Role of Vitamin A in Retinal Diseases.International journal of molecular sciences · 2022Review
- An Overview of the Genetics ofGenes · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeExcessive accumulation of lipofuscin is associated with pathogenesis of atrophic age-related macular degeneration (AMD) and Stargardt disease. Pharmacologic inhibition of the retinol-induced interaction of retinol-binding protein 4 (RBP4) with transthyretin (TTR) in the serum may decrease the uptake of serum retinol to the retina and reduce formation of lipofuscin bisretinoids. We evaluated in vitro and in vivo properties of the new nonretinoid RBP4 antagonist, A1120.
methodsRBP4 binding potency, ability to antagonize RBP4-TTR interaction, and compound specificity were analyzed for A1120 and for the prototypic RBP4 antagonist fenretinide. A1120 ability to inhibit RPE65-mediated isomerohydrolase activity was assessed in the RPE microsomes. The in vivo effect of A1120 administration on serum RBP4, visual cycle retinoids, lipofuscin bisretinoids, and retinal visual function was evaluated using a combination of biochemical and electrophysiologic techniques.
resultsIn comparison to fenretinide, A1120 did not act as a RARα agonist, while exhibiting superior in vitro potency in RBP4 binding and RBP4-TTR interaction assays. A1120 did not inhibit isomerohydrolase activity in the RPE microsomes. A1120 dosing in mice induced 75% reduction in serum RBP4, which correlated with reduction in visual cycle retinoids and ocular levels of lipofuscin fluorophores. A1120 dosing did not induce changes in kinetics of dark adaptation.
conclusionsA1120 significantly reduces accumulation of lipofuscin bisretinoids in the Abca4(-/-) animal model. This activity correlates with reduction in serum RBP4 and visual cycle retinoids confirming the mechanism of action for A1120. In contrast to fenretinide, A1120 does not act as a RARα agonist indicating a more favorable safety profile for this nonretinoid compound.
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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.