ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Receptor interacting protein kinase-mediated necrosis contributes to cone and rod photoreceptor degeneration in the retina lacking interphotoreceptor retinoid-binding protein.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 94 citations in OpenAlex.
- RGR-Mediated Photopic Visual Cycle and Oxidative Stress: Potential Mechanisms for Cone Vision Impairment and Retinal Degeneration in Retinitis Pigmentosa Linked to D1080N-IRBP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Retinol-binding protein 3 in ophthalmology: current evidence, research progress, and future perspectives.Frontiers in immunology · 2026Review
- AAV2-driven endothelin induces chronic reduced retinal blood flow/retinal ganglion cell loss in rats.Life science alliance · 2025Article
- Autophagy disruption and mitochondrial stress precede photoreceptor necroptosis in multiple mouse models of inherited retinal disorders.Nature communications · 2025Article
- Mechanisms of retinal photoreceptor loss in spontaneously hypertensive rats.Experimental eye research · 2024Article
- Ablation of Fatty Acid Transport Protein-4 Enhances Cone Survival, M-cone Vision, and Synthesis of Cone-Tropic 9-The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- SH-SY5Y human neuronal cells with mutations of theBiochemistry and biophysics reports · 2024Article
- Non-Apoptotic Programmed Cell Death as Targets for Diabetic Retinal Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Identification of the zebrafish homologues of IMPG2, a retinal proteoglycan.Cell and tissue research · 2023Article
- Article
- DPP-4 Inhibitors Attenuate Fibrosis After Glaucoma Filtering Surgery by Suppressing the TGF-β/Smad Signaling Pathway.Investigative ophthalmology & visual science · 2023Article
- Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.International journal of molecular sciences · 2023Article
- Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases.International journal of biological sciences · 2023Review
- Novel compound heterozygous variants in theFrontiers in cell and developmental biology · 2023Article
- Rapamycin Inhibits Light-Induced Necrosome Activation Occurring in Wild-Type, but not RPE65-Null, Mouse Retina.Investigative ophthalmology & visual science · 2022Article
- Neuroprotection for Age-Related Macular Degeneration.Ophthalmology science · 2022Review
- Identification of Interphotoreceptor retinoid-binding protein in the Schisis cavity fluid of a patient with congenital X-linked Retinoschisis.BMC ophthalmology · 2022Article
- Slow Resting State Fluctuations Enhance Neuronal and Behavioral Responses to Looming Sounds.Brain topography · 2022Article
- Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.Frontiers in immunology · 2022Review
- Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma.Frontiers in immunology · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Interphotoreceptor retinoid-binding protein (IRBP) secreted by photoreceptors plays a pivotal role in photoreceptor survival with an unknown mechanism. A mutation in the human IRBP has been linked to retinitis pigmentosa, a progressive retinal degenerative disease. Mice lacking IRBP display severe early and progressive photoreceptor degeneration. However, the signaling pathway(s) leading to photoreceptor death in IRBP-deficient mice remains poorly understood. Here, we show that amounts of tumor necrosis factor-α (TNF-α) in the interphotoreceptor matrix and retinas of Irbp(-/-) mice were increased more than 10-fold and fivefold, respectively, compared with those in wild-type mice. Moreover, TNF-α receptor 1, an important membrane death receptor that mediates both programmed apoptosis and necrosis, was also significantly increased in Irbp(-/-) retina, and was colocalized with peanut agglutinin to the Irbp(-/-) cone outer segments. Although these death signaling proteins were increased, the caspase-dependent and independent apoptotic pathways were mildly activated in the Irbp(-/-) retinas, suggesting that other cell death mechanism(s) also contributes to the extensive photoreceptor degeneration in Irbp(-/-) retina. We found that receptor interacting protein 1 and 3 (RIP1 and RIP3) kinases, the intracellular key mediators of TNF-induced cellular necrosis, were elevated at least threefold in the Irbp(-/-) retinas. Moreover, pharmacological inhibition of RIP1 kinase significantly prevented cone and rod photoreceptor degeneration in Irbp(-/-) mice. These results reveal that RIP kinase-mediated necrosis strongly contributes to cone and rod degeneration in Irbp(-/-) mice, implicating the TNF-RIP pathway as a potential therapeutic target to prevent or delay photoreceptor degeneration in patients with retinitis pigmentosa caused by IRBP mutation.
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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.