ArticlePLoS biology2025
Discovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa.
Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed.
- Conformational signatures of native ligand and pharmacochaperone binding in rhodopsin.Structure (London, England : 1993) · 2026Article
- Dual Targeting of Galanin Receptor 3 Signaling and Redox Homeostasis Enhances Photoreceptor Survival in Retinas ofAntioxidants (Basel, Switzerland) · 2026Article
- A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction.Science advances · 2026Article
- Inhibition of galanin receptor 3 slows down retina degeneration in retinitis pigmentosa through modulation of inflammatory and oxidative stress response.Scientific reports · 2026Article
- Therapeutic Potential of Partial Retinoid Agonists against Vertebrate Rhodopsin Misfolding Disorders.ACS omega · 2025Article
- Small-Molecule Ligands of Rhodopsin and Their Therapeutic Potential in Retina Degeneration.International journal of molecular sciences · 2025Review
- Unifying perspectives on the activity and genotypic targeting of pharmacological chaperones.The Journal of biological chemistry · 2025Review
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Pathogenic mutations that cause rhodopsin misfolding lead to a spectrum of currently untreatable blinding diseases collectively termed retinitis pigmentosa. Small molecules to correct rhodopsin misfolding are therefore urgently needed. In this study, we utilized virtual screening to search for drug-like molecules that bind to the orthosteric site of rod opsin and improve its folding and trafficking. We identified and validated the biological effects of 2 non-retinoid compounds with favorable pharmacological properties that cross the blood-retina barrier. These compounds reversibly bind to unliganded rod opsin, each with a Kd comparable to 9-cis-retinal and improve opsin stability. By improving the internal protein structure network (PSN), these rod opsin ligands also enhanced the plasma membrane expression of total 36 of 123 tested clinical RP variants, including the most prevalent P23H variant. Importantly, these compounds protected retinas against light-induced degeneration in mice vulnerable to bright light injury and prolonged survival of photoreceptors in a retinitis pigmentosa mouse model for rod opsin misfolding.
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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.