ArticleCell death & disease2018
Pigment epithelium-derived factor hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
- Mechanistic insights into the role of PEDF-R (PNPLA2) in photoreceptors.Bioscience reports · 2026Review
- Complexity of PEDF multifunctional signaling in retinal development and diseases.Communications biology · 2026Article
- Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.Genes · 2026Review
- Extracellular matrix stiffness modulates angiogenic properties of the retinal pigment epithelium.Scientific reports · 2025Article
- Pigment Epithelium-Derived Factor (PEDF)-Based Therapy Induced Photoreceptor Survival by Stabilizing Choroidal Neovessels in a VEGF Overexpression CNV Rat Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Role of PEDF in the Eye, Bone, and Nervous and Immune Systems.Pharmaceutics · 2025Review
- A role of pigment epithelium-derived factor in zinc-mediated mechanism of neurodegeneration in glaucoma.Communications biology · 2025Article
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.Communications medicine · 2025Article
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.bioRxiv : the preprint server for biology · 2024Article
- PEDF protects retinal pigment epithelium from ferroptosis and ameliorates dry AMD-like pathology in a murine model.GeroScience · 2024Article
- T-type voltage-gated channels, NaCell communication and signaling : CCS · 2024Article
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- Ablation of pigment epithelium-derived factor receptor (PEDF-R/Pnpla2) causes photoreceptor degeneration.Journal of lipid research · 2023Article
- Interaction network of extracellular vesicles building universal analysis via eye tears: iNEBULA.Science advances · 2023Article
- Expression and production of pigment epithelium-derived factor (PEDF) and PEDF receptor variants from mammalian and bacterial cells.Protein expression and purification · 2022Article
- Human iPSC- and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2022Article
- Primary and Secondary Cone Cell Death Mechanisms in Inherited Retinal Diseases and Potential Treatment Options.International journal of molecular sciences · 2022Review
- Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization.Journal of diabetes research · 2022Article
- AMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration.Communications biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Calcium ions play a critical role in neuronal cell death. Pigment epithelium-derived factor (PEDF) is a promising neuroprotective protein for photoreceptor cells but the mechanisms mediating its effects against retinal degeneration are still not well characterized. We addressed this question in the rd1 degenerating mouse retina that bears a mutation in the Pde6b gene encoding one subunit of the phosphodiesterase enzyme. Loss of phosphodiesterase activity in rod photoreceptor cells increases cyclic guanosine monophosphate (cGMP) levels leading to a rise in intracellular calcium. Short-term treatments with recombinant human PEDF protein decreased intracellular calcium in photoreceptors in vivo. Taking advantage of calcium pump blockers, we defined that PEDF signaling acts on PMCA calcium pumps to lower intracellular calcium. PEDF restrained cell death pathways activated by high calcium levels and engaging calpains, BAX and AIF. The neurotrophic effects were mediated by the PEDF receptor (PEDF-R), encoded by the PNPLA2 gene. Finally, peptides containing the neurotrophic domain of PEDF targeted these same cell death pathways in vivo. The findings reveal rescue from death of degenerating photoreceptor cells by a PEDF-mediated preservation of intracellular calcium homeostasis.
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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.