ArticleCell death & disease2016
Unfolded protein response-induced dysregulation of calcium homeostasis promotes retinal degeneration in rat models of autosomal dominant retinitis pigmentosa.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.npj aging · 2026Review
- Pharmacological and Safety Evaluation of the Small Molecule MP-004 Following Topical Ocular Administration for the Treatment of Inherited Retinal Dystrophies.Drug design, development and therapy · 2026Article
- Topical Administration of Novel FKBP12 Ligand MP-004 Improves Retinal Function and Structure in Retinitis Pigmentosa Models.Investigative ophthalmology & visual science · 2025Article
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- Selective Assembly of TRPC Channels in the Rat Retina during Photoreceptor Degeneration.International journal of molecular sciences · 2024Article
- NUDC is critical for rod photoreceptor function, maintenance, and survival.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The Clock:Cycle complex is a major transcriptional regulator of Drosophila photoreceptors that protects the eye from retinal degeneration and oxidative stress.PLoS genetics · 2022Article
- Microtubule modification defects underlie cilium degeneration in cell models of retinitis pigmentosa associated with pre-mRNA splicing factor mutations.Frontiers in genetics · 2022Article
- Cellular and molecular alterations in neurons and glial cells in inherited retinal degeneration.Frontiers in neuroanatomy · 2022Review
- A Pipeline for Natural Small Molecule Inhibitors of Endoplasmic Reticulum Stress.Frontiers in pharmacology · 2022Article
- Tribbles homolog 3-mediated targeting the AKT/mTOR axis in mice with retinal degeneration.Cell death & disease · 2021Article
- Calcineurin Activity Is Increased in Charcot-Marie-Tooth 1B Demyelinating Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 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
- The Alter Retina: Alternative Splicing of Retinal Genes in Health and Disease.International journal of molecular sciences · 2021Review
- Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases.Progress in retinal and eye research · 2020Review
- Targeting molecular pathways for the treatment of inherited retinal degeneration.Neural regeneration research · 2020Review
- Copper induce zebrafish retinal developmental defects via triggering stresses and apoptosis.Cell communication and signaling : CCS · 2020Article
- Mutation spectrum of PRPF31, genotype-phenotype correlation in retinitis pigmentosa, and opportunities for therapy.Experimental eye research · 2020Review
- Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis.Cell cycle (Georgetown, Tex.) · 2019Article
- Live-Cell Assays for Cell Stress Responses Reveal New Patterns of Cell Signaling Caused by Mutations in Rhodopsin, α-Synuclein and TDP-43.Frontiers in cellular neuroscience · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanism of autosomal dominant retinitis pigmentosa (ADRP) in rats is closely associated with a persistently activated unfolded protein response (UPR). If unchecked, the UPR might trigger apoptosis, leading to photoreceptor death. One of the UPR-activated cellular signaling culminating in apoptotic photoreceptor cell death is linked to an increase in intracellular Ca(2+). Therefore, we validated whether ADRP retinas experience a cytosolic Ca(2+) overload, and whether sustained UPR in the wild-type retina could promote retinal degeneration through Ca(2+)-mediated calpain activation. We performed an ex vivo experiment to measure intracellular Ca(2+) in ADRP retinas as well as to detect the expression levels of proteins that act as Ca(2+) sensors. In separate experiments with the subretinal injection of tunicamycin (UPR inducer) and a mixture of calcium ionophore (A231278) and thapsigargin (SERCA2b inhibitor) we assessed the consequences of a sustained UPR activation and increased intracellular Ca(2+) in the wild-type retina, respectively, by performing scotopic ERG, histological, and western blot analyses. Results of the study revealed that induced UPR in the retina activates calpain-mediated signaling, and increased intracellular Ca(2+) is capable of promoting retinal degeneration. A significant decline in ERG amplitudes at 6 weeks post treatment was associated with photoreceptor cell loss that occurred through calpain-activated CDK5-pJNK-Csp3/7 pathway. Similar calpain activation was found in ADRP rat retinas. A twofold increase in intracellular Ca(2+) and up- and downregulations of ER membrane-associated Ca(2+)-regulated IP3R channels and SERCA2b transporters were detected. Therefore, sustained UPR activation in the ADRP rat retinas could promote retinal degeneration through increased intracellular Ca(2+) and calpain-mediated apoptosis.
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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.