ArticleBrain : a journal of neurology2014
Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling.
Article in Brain : a journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Mitochondrial Homeostasis Mediates the Sustained Neuroprotection of CNTF-Chitosan Hydrogel Against NMDA-Induced Retinal Ganglion Cell Excitotoxicity.International journal of molecular sciences · 2026Article
- Ciliary neurotrophic factor (CNTF) contributes to pelvic organ prolapse by modulating collagen expression via the JAK2-STAT3 pathway.Journal of molecular histology · 2025Article
- A cross-tissue transcriptome-wide association study identified susceptibility genes for age-related macular degeneration.Scientific reports · 2025Article
- Caspase-mediated pathways in retinal ganglion cell injury: a novel therapeutic target for glaucoma.Frontiers in cell and developmental biology · 2025Review
- Knocking down tumor suppressor gene PTPRG enhances axonal regeneration of dorsal root ganglion neurons.Frontiers in cell and developmental biology · 2025Article
- Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration.International journal of molecular sciences · 2024Review
- Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).Molecular medicine reports · 2024Review
- Inhibition of miR-144-3p/FOXO1 Attenuates Diabetic Keratopathy Via Modulating Autophagy and Apoptosis.Investigative ophthalmology & visual science · 2024Article
- Aging Effects on Optic Nerve Neurodegeneration.International journal of molecular sciences · 2023Review
- Optic Nerve Crush Injury in Rodents to Study Retinal Ganglion Cell Neuroprotection and Regeneration.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Preparation of Retinal Explant Cultures.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline.Cell death & disease · 2022Article
- Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury.Science advances · 2022Article
- A humble neuroanatomist: Martin Berry, PhD (1936-2021).The European journal of neuroscience · 2022Article
- The neuroprotective effect of melatonin in glutamate excitotoxicity of R28 cells and mouse retinal ganglion cells.Frontiers in endocrinology · 2022Article
- Article
- Identification of a Novel Pyroptosis-Related Gene Signature Indicative of Disease Prognosis and Treatment Response in Skin Cutaneous Melanoma.International journal of general medicine · 2022Article
- Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma.Scientific reports · 2021Article
- Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury.Cells · 2021Article
- Advances in Regeneration of Retinal Ganglion Cells and Optic Nerves.International journal of molecular sciences · 2021Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
We have previously shown that crushing the optic nerve induces death of retinal ganglion cells by apoptosis, but suppression of CASP2, which is predominantly activated in retinal ganglion cells, using a stably modified short interfering RNA CASP2, inhibits retinal ganglion cell apoptosis. Here, we report that combined delivery of short interfering CASP2 and inhibition of CASP6 using a dominant negative CASP6 mutant activates astrocytes and Müller cells, increases CNTF levels in the retina and leads to enhanced retinal ganglion cell axon regeneration. In dissociated adult rat mixed retinal cultures, dominant negative CASP6 mutant + short interfering CASP2 treatment also significantly increases GFAP+ glial activation, increases the expression of CNTF in culture, and subsequently increases the number of retinal ganglion cells with neurites and the mean retinal ganglion cell neurite length. These effects are abrogated by the addition of MAB228 (a monoclonal antibody targeted to the gp130 component of the CNTF receptor) and AG490 (an inhibitor of the JAK/STAT pathway downstream of CNTF signalling). Similarly, in the optic nerve crush injury model, MAB228 and AG490 neutralizes dominant negative CASP6 mutant + short interfering CASP2-mediated retinal ganglion cell axon regeneration, Müller cell activation and CNTF production in the retina without affecting retinal ganglion cell survival. We therefore conclude that axon regeneration promoted by suppression of CASP2 and CASP6 is CNTF-dependent and mediated through the JAK/STAT signalling pathway. This study offers insights for the development of effective therapeutics for promoting retinal ganglion cell survival and axon regeneration.
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