ArticleThe Journal of clinical investigation2015
Molecular pharmacodynamics of emixustat in protection against retinal degeneration.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 72 citations in OpenAlex.
- Visual cycle-derived bisretinoids as endogenous natural products: enzyme-free formation, photochemical reactivity, and retinal degeneration.Natural product reports · 2026Review
- Light-Activated RPE65 Inhibitors Enable On-Demand Visual Cycle Control.Journal of the American Chemical Society · 2026Article
- Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy.Biomolecules · 2025Review
- RPE65 Variant p.(E519K) Causes a Novel Dominant Adult-Onset Maculopathy in 83 Affected Individuals.Investigative ophthalmology & visual science · 2025Article
- Bisretinoid lipofuscin, fundus autofluorescence and retinal disease.Progress in retinal and eye research · 2025Review
- 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
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Advances and therapeutic opportunities in visual cycle modulation.Progress in retinal and eye research · 2025Review
- Photoprotective Effects of Phytochemicals on Blue Light-Induced Retinal Damage: Current Evidence and Future Perspectives.Nutrients · 2025Review
- Crocin Protects the 661W Murine Photoreceptor Cell Line against the Toxic Effects of All-International journal of molecular sciences · 2024Article
- Tuning the Metabolic Stability of Visual Cycle Modulators through Modification of an RPE65 Recognition Motif.Journal of medicinal chemistry · 2023Article
- From mouse to human: Accessing the biochemistry of vision in vivo by two-photon excitation.Progress in retinal and eye research · 2023Review
- Towards a New Biomarker for Diabetic Retinopathy: Exploring RBP3 Structure and Retinoids Binding for Functional Imaging of Eyes In Vivo.International journal of molecular sciences · 2023Review
- An inducible amphipathic α-helix mediates subcellular targeting and membrane binding of RPE65.Life science alliance · 2023Article
- Electroretinography as a Biomarker to Monitor the Progression of Stargardt Disease.International journal of molecular sciences · 2022Article
- Recent Advances in Age-Related Macular Degeneration Therapies.Molecules (Basel, Switzerland) · 2022Review
- Retinal pigment epithelium 65 kDa protein (RPE65): An update.Progress in retinal and eye research · 2022Review
- The Role of Vitamin A in Retinal Diseases.International journal of molecular sciences · 2022Review
- The novel visual cycle inhibitor (±)-RPE65-61 protects retinal photoreceptors from light-induced degeneration.PloS one · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators.
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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.