ArticleCell death & disease2018
Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signaling.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 165 citations in OpenAlex.
- Modalities of vision restoration in optic neuropathies and retinal disease.Progress in retinal and eye research · 2026Review
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Targeting Sensory Neuropathies Through Neurotrophin-Based Approaches.Cellular and molecular neurobiology · 2026Review
- Extracellular vesicles as therapeutic agents for retinal ganglion cell degeneration: current challenges and future prospects.International ophthalmology · 2026Review
- Strategic lipid nanoparticle design dictates retinal delivery post inner limiting membrane disruption.Drug delivery and translational research · 2026Article
- Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.Genes · 2026Review
- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- The therapeutic potential of bone marrow mesenchymal stem cells-derived exosomes for retinal and optic nerve diseases.Frontiers in cell and developmental biology · 2026Review
- Role of BDNF in form-deprivation myopia progression in guinea pigs.Frontiers in immunology · 2026Article
- Article
- Research progress on molecular therapy for glaucoma (Review).Molecular medicine reports · 2026Review
- Novel insights into β3-adrenoceptor function in a model of retinopathy of prematurity: the contribution of astrocytes to retinal protection.Frontiers in neuroscience · 2026Article
- Crosstalk Between Neuronal and Glial Cells in Diabetic Retinopathy: Mechanisms and Implications for Neurodegeneration.Molecular neurobiology · 2025Review
- Sustained Neurotrophic Factor Co-Treatment Enhances Donor and Host Retinal Ganglion Cell Survival in Mice.Translational vision science & technology · 2025Article
- Brain Neurotrophins and Plant Polyphenols: A Powerful Connection.Molecules (Basel, Switzerland) · 2025Review
- Variations in Intraocular Pressure Among Athletes Across Different Sports Disciplines.Journal of clinical medicine · 2025Article
- Targeted Neuroprotection of Retinal Ganglion Cells Via AAV2-hSyn-NGF Gene Therapy in Glaucoma Models.Investigative ophthalmology & visual science · 2025Article
- The molecular mechanisms underlying retinal ganglion cell apoptosis and optic nerve regeneration in glaucoma (Review).International journal of molecular medicine · 2025Review
- Retina-Targeted 17β-Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Networks After Optic Nerve Crush in a Rat Model of Surgical Menopause.International journal of molecular sciences · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Previous studies have demonstrated that intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury. BDNF gene therapy can improve RGC survival in experimental models of glaucoma, the leading cause of irreversible blindness worldwide. However, the therapeutic efficacy of BDNF supplementation alone is time limited at least in part due to BDNF receptor downregulation. Tropomyosin-related receptor kinase-B (TrkB) downregulation has been reported in many neurological diseases including glaucoma, potentially limiting the effect of sustained or repeated BDNF delivery.Here, we characterize a novel adeno-associated virus (AAV) gene therapy (AAV2 TrkB-2A-mBDNF) that not only increases BDNF production but also improves long-term neuroprotective signaling by increasing expression of the BDNF receptor (TrkB) within the inner retina. This approach leads to significant and sustained elevation of survival signaling pathways ERK and AKT within RGCs over 6 months and avoids the receptor downregulation which we observe with treatment with AAV2 BDNF alone. We validate the neuroprotective efficacy of AAV2 TrkB-2A-mBDNF in a mouse model of optic nerve injury, where it outperforms conventional AAV2 BDNF or AAV2 TrkB therapy, before showing powerful proof of concept neuroprotection of RGCs and axons in a rat model of chronic intraocular pressure (IOP) elevation. We also show that there are no adverse effects of the vector on retinal structure or function as assessed by histology and electroretinography in young or aged animals. Further studies are underway to explore the potential of this vector as a candidate for progression into clinical studies to protect RGCs in patients with glaucoma and progressive visual loss despite conventional IOP-lowering treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.