ArticleScience signaling2016
Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 39 citations in OpenAlex.
- Altered Retinal Dopamine Homeostasis in Murine Models of Retinitis Pigmentosa.Journal of neurochemistry · 2026Article
- Cyclic nucleotide signaling as a drug target in retinitis pigmentosa.FEBS letters · 2025Review
- Effects of taurine, brimonidine and betaxolol on oscillation modulation and stimulation efficiency in degenerated rd10 mouse retinas.Scientific reports · 2025Article
- A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models.Nature communications · 2024Article
- Synthesis and Biological Analysis of Iso-dimethyltryptamines in a Model of Light-Induced Retinal Degeneration.ACS medicinal chemistry letters · 2024Article
- Melanopsin-mediated optical entrainment regulates circadian rhythms in vertebrates.Communications biology · 2023Review
- Ginsenoside Re Mitigates Photooxidative Stress-Mediated Photoreceptor Degeneration and Retinal Inflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Single Cell RNA Sequencing Analysis of Mouse Retina Identifies a Subpopulation of Muller Glia Involved in Retinal Recovery From Injury in the FCD-LIRD Model.Investigative ophthalmology & visual science · 2023Article
- Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Galanin receptor 3 - A new pharmacological target in retina degeneration.Pharmacological research · 2023Article
- GPCR systems pharmacology: a different perspective on the development of biased therapeutics.American journal of physiology. Cell physiology · 2022Review
- Cuscuta chinensis Lam. Protects Against Light-Induced Retinal Degeneration: Therapeutic Implications for Photoreceptor Degenerative Disorders.Frontiers in pharmacology · 2022Article
- Astragaloside A Protects Against Photoreceptor Degeneration in Part Through Suppressing Oxidative Stress and DNA Damage-Induced Necroptosis and Inflammation in the Retina.Journal of inflammation research · 2022Article
- Regulation of Adrenergic, Serotonin, and Dopamine Receptors to Inhibit Diabetic Retinopathy: Monotherapies versus Combination Therapies.Molecular pharmacology · 2021Article
- Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.Scientific reports · 2021Article
- Epigenetic hallmarks of age-related macular degeneration are recapitulated in a photosensitive mouse model.Human molecular genetics · 2020Article
- Retinal disease in ciliopathies: Recent advances with a focus on stem cell-based therapies.Translational science of rare diseases · 2019Article
- The selective estrogen receptor modulator raloxifene mitigates the effect of all-The Journal of biological chemistry · 2019Article
- A Mixture of U.S. Food and Drug Administration-Approved Monoaminergic Drugs Protects the Retina From Light Damage in Diverse Models of Night Blindness.Investigative ophthalmology & visual science · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Photoreceptor cell degeneration leads to visual impairment and blindness in several types of retinal disease. However, the discovery of safe and effective therapeutic strategies conferring photoreceptor cell protection remains challenging. Targeting distinct cellular pathways with low doses of different drugs that produce a functionally synergistic effect could provide a strategy for preventing or treating retinal dystrophies. We took a systems pharmacology approach to identify potential combination therapies using a mouse model of light-induced retinal degeneration. We showed that a combination of U.S. Food and Drug Administration-approved drugs that act on different G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) exhibited synergistic activity that protected retinas from light-induced degeneration even when each drug was administered at a low dose. In functional assays, the combined effects of these drugs were stimulation of Gi/o signaling by activating the dopamine receptors D2R and D4R, as well as inhibition of Gs and Gq signaling by antagonizing D1R and the α1A-adrenergic receptor ADRA1A, respectively. Moreover, transcriptome analyses demonstrated that such combined GPCR-targeted treatments preserved patterns of retinal gene expression that were more similar to those of the normal retina than did higher-dose monotherapy. Our study thus supports a systems pharmacology approach to identify treatments for retinopathies, an approach that could extend to other complex disorders.
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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.