ArticleBrain : a journal of neurology2018
Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 79 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.
Safety of Topical Insulin Eye Drops for the Treatment of Open-angle Glaucoma
A Phase 1/2 Dose Escalation Followed by a Masked, Randomized, Placebo-Controlled Study to Evaluate Topical Insulin for Neuroprotection in Open Angle Glaucoma
Who cites it
79 citing papers in PubMed.
- A Phase I Randomized Trial of Topical Insulin for Glaucoma: Safety and Efficacy Outcomes.Ophthalmology science · 2026Article
- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Prospects for Neuroprotective Therapies in Glaucoma: Drug Targets and Emerging Clinical Strategies.Drug design, development and therapy · 2026Review
- Human pluripotent stem cell-derived retinal ganglion cells: advances in differentiation and translational applications.Molecular medicine (Cambridge, Mass.) · 2025Review
- Injury-induced nuclear export of RNA-binding proteins drives mRNA stabilization and translation to promote dendrite regeneration.bioRxiv : the preprint server for biology · 2025Article
- Article
- Insulin-Enhanced Biological Visual Rehabilitation in Neuroretinal Degeneration Patients Treated with Mesenchymal Cell-Derived Secretome.Pharmaceutics · 2025Article
- Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion.Communications biology · 2025Article
- Lithium normalizes ASD-related neuronal, synaptic, and behavioral phenotypes in DYRK1A-knockin mice.Molecular psychiatry · 2025Article
- A systematic review of in vivo brain insulin resistance biomarkers in humans.Biomarkers in neuropsychiatry · 2025Review
- Spatiotemporal Expression of IRS-1 During Brain Development and its Role in Neural Stem Cell Differentiation.Neuromolecular medicine · 2025Article
- Independent control of functional rewiring after axon injury byJournal of biosciences · 2025Article
- Article
- Retinal Ganglion Cell Replacement in Glaucoma Therapy: A Narrative Review.Journal of clinical medicine · 2024Review
- Dendrite injury triggers neuroprotection in Drosophila models of neurodegenerative disease.Scientific reports · 2024Article
- Loss of Stim2 in zebrafish induces glaucoma-like phenotype.Scientific reports · 2024Article
- Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.Acta neuropathologica communications · 2024Article
- Advances in Neuroprotection in Glaucoma: Pharmacological Strategies and Emerging Technologies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Membrane-anchored intracellular insulin receptor or insulin-like growth factor-1 receptor elicits ligand-independent downstream signaling.Biochemistry and biophysics reports · 2024Article
- Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
6 authors.
Funding
Abstract
Dendrite pathology and synapse disassembly are critical features of chronic neurodegenerative diseases. In spite of this, the capacity of injured neurons to regenerate dendrites has been largely ignored. Here, we show that, upon axonal injury, retinal ganglion cells undergo rapid dendritic retraction and massive synapse loss that preceded neuronal death. Human recombinant insulin, administered as eye drops or systemically after dendritic arbour shrinkage and prior to cell loss, promoted robust regeneration of dendrites and successful reconnection with presynaptic targets. Insulin-mediated regeneration of excitatory postsynaptic sites on retinal ganglion cell dendritic processes increased neuronal survival and rescued light-triggered retinal responses. Further, we show that axotomy-induced dendrite retraction triggered substantial loss of the mammalian target of rapamycin (mTOR) activity exclusively in retinal ganglion cells, and that insulin fully reversed this response. Targeted loss-of-function experiments revealed that insulin-dependent activation of mTOR complex 1 (mTORC1) is required for new dendritic branching to restore arbour complexity, while complex 2 (mTORC2) drives dendritic process extension thus re-establishing field area. Our findings demonstrate that neurons in the mammalian central nervous system have the intrinsic capacity to regenerate dendrites and synapses after injury, and provide a strong rationale for the use of insulin and/or its analogues as pro-regenerative therapeutics for intractable neurodegenerative diseases including glaucoma.
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.