ArticleFrontiers in cellular neuroscience2014
Viral vector-mediated downregulation of RhoA increases survival and axonal regeneration of retinal ganglion cells.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Recent progress of principal techniques used in the study of Müller glia reprogramming in mice.Cell regeneration (London, England) · 2024Review
- Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.NPJ Regenerative medicine · 2024Article
- Article
- Review
- Planet of the AAVs: The Spinal Cord Injury Episode.Biomedicines · 2021Review
- AAV-mediated inhibition of ULK1 promotes axonal regeneration in the central nervous system in vitro and in vivo.Cell death & disease · 2021Article
- Immunological and molecular basics of the primary open angle glaucoma pathomechanism.Central-European journal of immunology · 2021Review
- Molecular Mechanisms of Central Nervous System Axonal Regeneration and Remyelination: A Review.International journal of molecular sciences · 2020Review
- Axonal Development: RhoA Restrains but Does Not Specify.Current biology : CB · 2019Article
- Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer.Stem cell research & therapy · 2018Article
- RhoA activation in axotomy-induced neuronal death.Experimental neurology · 2018Article
- A Repulsive Environment Induces Neurodegeneration of Midbrain Dopaminergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- TGF-β-induced IOP elevations are mediated by RhoA in the early but not the late fibrotic phase of open angle glaucoma.Molecular vision · 2018Article
- Optic nerve regeneration in the mouse is a complex trait modulated by genetic background.Molecular vision · 2018Article
- A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice.Scientific reports · 2017Article
- Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury.Experimental eye research · 2017Article
- Role of the Rho GTPase/Rho kinase signaling pathway in pathogenesis and treatment of glaucoma: Bench to bedside research.Experimental eye research · 2017Review
- RhoA as a target to promote neuronal survival and axon regeneration.Neural regeneration research · 2017Review
- Gene Manipulation Strategies to Identify Molecular Regulators of Axon Regeneration in the Central Nervous System.Frontiers in cellular neuroscience · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Rho/ROCK pathway is a promising therapeutic target in neurodegenerative and neurotraumatic diseases. Pharmacological inhibition of various pathway members has been shown to promote neuronal regeneration and survival. However, because pharmacological inhibitors are inherently limited in their specificity, shRNA-mediated approaches can add more information on the function of each single kinase involved. Thus, we generated adeno-associated viral vectors (AAV) to specifically downregulate Ras homologous member A (RhoA) via shRNA. We found that specific knockdown of RhoA promoted neurite outgrowth of retinal ganglion cells (RGC) grown on the inhibitory substrate chondroitin sulfate proteoglycan (CSPG) as well as neurite regeneration of primary midbrain neurons (PMN) after scratch lesion. In the rat optic nerve crush (ONC) model in vivo, downregulation of RhoA significantly enhanced axonal regeneration compared to control. Moreover, survival of RGC transduced with AAV expressing RhoA-shRNA was substantially increased at 2 weeks after optic nerve axotomy. Compared to previous data using pharmacological inhibitors to target RhoA, its upstream regulator Nogo or its main downstream target ROCK, the specific effects of RhoA downregulation shown here were most pronounced in regard to promoting RGC survival but neurite outgrowth and axonal regeneration were also increased significantly. Taken together, we show here that specific knockdown of RhoA substantially increases neuronal survival after optic nerve axotomy and modestly increases neurite outgrowth in vitro and axonal regeneration after optic nerve crush.
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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.