ArticleMolecular neurobiology2020
Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Enhanced Endocytosis and Mitochondrial Stress Underlie Severe Retinitis Pigmentosa With RHO P347L Mutant.Investigative ophthalmology & visual science · 2026Article
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.Communications medicine · 2025Article
- miR-429 RNA therapy as generic strategy to protect against photoreceptor loss.Molecular therapy. Nucleic acids · 2025Article
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.bioRxiv : the preprint server for biology · 2024Article
- Aggregation of rhodopsin mutants in mouse models of autosomal dominant retinitis pigmentosa.Nature communications · 2024Article
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Bridging the gap of vision restoration.Frontiers in cellular neuroscience · 2024Review
- cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023Review
- Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies.Frontiers in neuroscience · 2023Review
- GADD34 Ablation Exacerbates Retinal Degeneration in P23H RHO Mice.International journal of molecular sciences · 2022Article
- Subcellular localization of mutant P23H rhodopsin in an RFP fusion knock-in mouse model of retinitis pigmentosa.Disease models & mechanisms · 2022Article
- Article
- Visualizing Cell Death in Live Retina: Using Calpain Activity Detection as a Biomarker for Retinal Degeneration.International journal of molecular sciences · 2022Article
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- Loss of αA or αB-Crystallin Accelerates Photoreceptor Cell Death in a Mouse Model of P23H Autosomal Dominant Retinitis Pigmentosa.International journal of molecular sciences · 2021Article
- Neuroinflammation as a Therapeutic Target in Retinitis Pigmentosa and Quercetin as Its Potential Modulator.Pharmaceutics · 2021Review
- New In Vitro Cellular Model for Molecular Studies of Retinitis Pigmentosa.International journal of molecular sciences · 2021Article
- 2,3,5,6-Tetramethylpyrazine protects retinal photoreceptors against endoplasmic reticulum stress by modulating ATF4-mediated inhibition of PRP aggregation.Journal of molecular medicine (Berlin, Germany) · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The majority of mutations in rhodopsin (RHO) cause misfolding of the protein and has been linked to degeneration of photoreceptor cells in the retina. A lot of attention has been set on targeting ER stress for the development of new therapies for inherited retinal degeneration caused by mutations in the RHO gene. Nevertheless, the cell death pathway activated by RHO misfolded protein is still debated. In this study, we analyzed the retina of the knock-in mouse expressing the P23H misfolded mutant RHO. We found persistent unfolded protein response (UPR) during degeneration. Interestingly, long-term stimulation of the PERK branch of ER stress had a protective effect by phosphorylating nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, associated with antioxidant responses. Otherwise, we provide evidence that increased intracellular calcium and activation of calpains strongly correlated with rod photoreceptor cell death. By blocking calpain activity, we significantly decreased the activation of caspase-7 and apoptosis-inducing factor (AIF), two cell death effectors, and cell demise, and effectively protected the retina from degeneration caused by the P23H dominant mutation in RHO.
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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.