ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Complement C3-Targeted Gene Therapy Restricts Onset and Progression of Neurodegeneration in Chronic Mouse Glaucoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 110 citations in OpenAlex.
- Targeting C3aR/STAT3 signaling attenuates neuroinflammation and reverses neurological impairment in Neuromyelitis optica.Fundamental research · 2026Article
- Glaucoma and Autoimmunity: Immunopathogenic Mechanisms and Emerging Immunomodulatory Therapies.Biomedicines · 2026Review
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- The utility of aqueous and serum apolipoprotein E and galectin-3 as biomarkers of neuroinflammation in glaucoma.Scientific reports · 2026Article
- Cell-intrinsic vulnerability and immune activation cooperate to drive degeneration in a mitochondrial complex I deficiency model of optic neuropathy.Journal of neuroinflammation · 2026Article
- Research Advances in Glanimal Models of Glaucoma: Exploring Multidimensional Mechanisms and Novel Therapeutic Strategies.Pharmaceutics · 2026Review
- Reactive oxygen species/hypoxia dual-responsive polymers combined with melatonin inhibited PANoptosis of retinal ganglion cells for acute glaucoma treatment.Theranostics · 2026Article
- Microglial regulation of synaptic plasticity in transsynaptic degeneration of glaucoma.Frontiers in neuroscience · 2026Review
- CXCR3 Deficiency Alleviates Retinal Ganglion Cell Loss by Regulating Neuron-Astrocyte Communication in a Mouse Model of Glaucoma.Investigative ophthalmology & visual science · 2025Article
- Functional significance of commonly regulated genes in mechanically and chemically induced retinal ganglion cell death in rat eyes.Scientific reports · 2025Article
- Clofarabine Enhances the Transduction Efficiency of Recombinant AAV2 in the Retina.Investigative ophthalmology & visual science · 2025Article
- Evaluating the Evidence for Neuroprotective and Axonal Regenerative Activities of Different Inflammatory Cell Types After Optic Nerve Injury.Molecular neurobiology · 2025Review
- Complement updates in optic neuritis.Frontiers in neurology · 2025Review
- Unraveling the immune response in optic nerve injury: implications for retinal ganglion cell protection.Frontiers in immunology · 2025Review
- Glial-mediated immune modulation in glaucomatous neurodegeneration: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice.Experimental eye research · 2024Article
- Advances in Neuroprotection in Glaucoma: Pharmacological Strategies and Emerging Technologies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.Journal of neuroinflammation · 2024Article
- Microglia phagocytic mechanisms: Development informing disease.Current opinion in neurobiology · 2024Review
- Complement regulation in the eye: implications for age-related macular degeneration.The Journal of clinical investigation · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Dysregulation of the complement system is implicated in neurodegeneration, including human and animal glaucoma. Optic nerve and retinal damage in glaucoma is preceded by local complement upregulation and activation, but whether targeting this early innate immune response could have therapeutic benefit remains undefined. Because complement signals through three pathways that intersect at complement C3 activation, here we targeted this step to restore complement balance in the glaucomatous retina and to determine its contribution to degeneration onset and/or progression. To achieve this, we combined adeno-associated virus retinal gene therapy with the targeted C3 inhibitor CR2-Crry. We show that intravitreal injection of AAV2.CR2-Crry produced sustained Crry overexpression in the retina and reduced deposition of the activation product complement C3d on retinal ganglion cells and the inner retina of DBA/2J mice. This resulted in neuroprotection of retinal ganglion cell axons and somata despite continued intraocular pressure elevation, suggesting a direct restriction of neurodegeneration onset and progression and significant delay to terminal disease stages. Our study uncovers a damaging effect of complement C3 or downstream complement activation in glaucoma, and it establishes AAV2.CR2-Crry as a viable therapeutic strategy to target pathogenic C3-mediated complement activation in the glaucomatous retina.
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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.