ArticlePloS one2012
Pharmacological inhibition of caspase-2 protects axotomised retinal ganglion cells from apoptosis in adult rats.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Peptide dendrimer and hyaluronic acid modified nanovesicles for ocular delivery of timolol maleate and siRNA.Scientific reports · 2025Article
- Caspase-mediated pathways in retinal ganglion cell injury: a novel therapeutic target for glaucoma.Frontiers in cell and developmental biology · 2025Review
- Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).Molecular medicine reports · 2024Review
- Regulated Cell Death of Retinal Ganglion Cells in Glaucoma: Molecular Insights and Therapeutic Potentials.Cellular and molecular neurobiology · 2023Review
- Targeting caspase-2 interactions with tau in Alzheimer's disease and related dementias.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Aging Effects on Optic Nerve Neurodegeneration.International journal of molecular sciences · 2023Review
- Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage.Neural regeneration research · 2021Article
- Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma.Scientific reports · 2021Article
- Mutant three-repeat tau expression initiates retinal ganglion cell death through Caspase-2.Neurobiology of disease · 2021Article
- Rapid assessment of ocular drug delivery in a novel ex vivo corneal model.Scientific reports · 2020Article
- The Role of Caspase-2 in Regulating Cell Fate.Cells · 2020Review
- Pigment epithelium-derived factor mediates retinal ganglion cell neuroprotection by suppression of caspase-2.Cell death & disease · 2019Article
- Optic nerve regeneration: A long view.Restorative neurology and neuroscience · 2019Review
- Modulation of the Immune System for the Treatment of Glaucoma.Current neuropharmacology · 2018Review
- Novel Therapeutics in Glaucoma Management.Current neuropharmacology · 2018Review
- The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market.Pharmaceutical research · 2017Review
- Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys.BioMed research international · 2017Article
- Epigenetics and Signaling Pathways in Glaucoma.BioMed research international · 2017Review
- Caspases in retinal ganglion cell death and axon regeneration.Cell death discovery · 2017Review
- Neural Stem Cell-based Intraocular Administration of Pigment Epithelium-derived Factor Promotes Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Crush Injury in Rat: An Experimental Study.Iranian journal of medical sciences · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Severing the axons of retinal ganglion cells (RGC) by crushing the optic nerve (ONC) causes the majority of RGC to degenerate and die, primarily by apoptosis. We showed recently that after ONC in adult rats, caspase-2 activation occurred specifically in RGC while no localisation of caspase-3 was observed in ganglion cells but in cells of the inner nuclear layer. We further showed that inhibition of caspase-2 using a single injection of stably modified siRNA to caspase-2 protected almost all RGC from death at 7 days, offering significant protection for up to 1 month after ONC. In the present study, we confirmed that cleaved caspase-2 was localised and activated in RGC (and occasional neurons in the inner nuclear layer), while TUNEL⁺ RGC were also observed after ONC. We then investigated if suppression of caspase-2 using serial intravitreal injections of the pharmacological inhibitor z-VDVAD-fmk (z-VDVAD) protected RGC from death for 15 days after ONC. Treatment of eyes with z-VDVAD suppressed cleaved caspase-2 activation by >85% at 3-4 days after ONC. Increasing concentrations of z-VDVAD protected greater numbers of RGC from death at 15 days after ONC, up to a maximum of 60% using 4000 ng/ml of z-VDVAD, compared to PBS treated controls. The 15-day treatment with 4000 ng/ml of z-VDVAD after ONC suppressed levels of cleaved caspase-2 but no significant changes in levels of cleaved caspase-3, -6, -7 or -8 were detected. Although suppression of caspase-2 protected 60% of RGC from death, RGC axon regeneration was not promoted. These results suggest that caspase-2 specifically mediates death of RGC after ONC and that suppression of caspase-2 may be a useful therapeutic strategy to enhance RGC survival not only after axotomy but also in diseases where RGC death occurs such as glaucoma and optic neuritis.
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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.