ArticleCell death & disease2019
Pigment epithelium-derived factor mediates retinal ganglion cell neuroprotection by suppression of caspase-2.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Evidence architecture of glaucoma-related biomaterials reveals an uneven transition toward smart materials, additive manufacturing, and functional tissue engineering.Frontiers in bioengineering and biotechnology · 2026Article
- Caspase-mediated pathways in retinal ganglion cell injury: a novel therapeutic target for glaucoma.Frontiers in cell and developmental biology · 2025Review
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- Microglial cGAS-STING signaling underlies glaucoma pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats.Journal of neuroinflammation · 2024Article
- Regulated Cell Death of Retinal Ganglion Cells in Glaucoma: Molecular Insights and Therapeutic Potentials.Cellular and molecular neurobiology · 2023Review
- The role of miRNA in retinal ganglion cell health and disease.Neural regeneration research · 2022Review
- Antibody and Protein Profiles in Glaucoma: Screening of Biomarkers and Identification of Signaling Pathways.Biology · 2021Review
- Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons.International journal of molecular sciences · 2020Article
- Human Mesenchymal Stem Cell Secretome Exhibits a Neuroprotective Effect overMolecular therapy. Methods & clinical development · 2020Article
- The Role of Caspase-2 in Regulating Cell Fate.Cells · 2020Review
- TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells.Investigative ophthalmology & visual science · 2020Article
- Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization.Oxidative medicine and cellular longevity · 2020Review
- Etomidate affects the anti-oxidant pathway to protect retinal ganglion cells after optic nerve transection.Neural regeneration research · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Retinal ganglion cells (RGCs) undergo rapid cell death by apoptosis after injury but can be rescued by suppression of caspase-2 (CASP2) using an siRNA to CASP2 (siCASP2). Pigment epithelium-derived factor (PEDF), has neuroprotective and anti-angiogenic functions and protects RGC from death. The purpose of this study was to investigate if suppression of CASP2 is a possible mechanism of neuroprotection by PEDF in RGC. Adult rat retinal cells were treated in vitro with sub-optimal and optimal concentrations of siCASP2 and PEDF and levels of CASP2 mRNA and RGC survival were then quantified. Optic nerve crush (ONC) injury followed by intravitreal injections of siCASP2 or PEDF and eye drops of PEDF-34 were also used to determine CASP2 mRNA and protein reduction. Results showed that PEDF and PEDF-34 significantly suppressed CASP2 mRNA in culture, by 1.85- and 3.04-fold, respectively, and increased RGC survival by 63.2 ± 3.8% and 81.9 ± 6.6%, respectively compared to cells grown in Neurobasal-A alone. RGC survival was significantly reduced in glial proliferation inhibited and purified RGC cultures suggesting that some of the effects of PEDF were glia-mediated. In addition, intravitreal injection of PEDF and eye drops of PEDF-34 after ONC also suppressed CASP2 mRNA levels by 1.82- and 3.89-fold and cleaved caspase-2 (C-CASP2) protein levels by 4.98- and 8.93-fold compared to ONC + PBS vehicle groups, respectively, without affecting other executioner caspases. Treatment of retinal cultures with PEDF and PEDF-34 promoted the secretion of neurotrophic factors (NTF) into the culture media, of which brain-derived neurotrophic factor (BDNF) caused the greatest reduction in CASP2 mRNA and C-CASP2 protein. The neuroprotective effects of PEDF were blocked by a polyclonal antibody and PEDF suppressed key elements in the apoptotic pathway. In conclusion, this study shows that some of the RGC neuroprotective effects of PEDF is regulated through suppression of CASP2 and downstream apoptotic signalling molecules.
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