ArticleJournal of neuroinflammation2016
Virus-mediated EpoR76E gene therapy preserves vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Genetic susceptibility and neuroprotective gene therapy of normal tension glaucoma: a review.Frontiers in medicine · 2026Review
- Intramuscular delivery of recombinant AAV expressing EpoR76E improves memory and is neuroprotective in 5xFAD transgenics.Research square · 2025Article
- Changes in the Protein Composition of the Aqueous Humor in Patients with Glaucoma: An Update Review.International journal of molecular sciences · 2025Review
- The role of RGC degeneration in the pathogenesis of glaucoma.International journal of biological sciences · 2025Review
- Challenging glaucoma with emerging therapies: an overview of advancements against the silent thief of sight.Frontiers in medicine · 2025Review
- Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma.International journal of molecular sciences · 2024Article
- Exploring dysfunctional barrier phenotypes associated with glaucoma using a human pluripotent stem cell-based model of the neurovascular unit.Fluids and barriers of the CNS · 2024Article
- Molecular pathways in experimental glaucoma models.Frontiers in neuroscience · 2024Review
- The concept of gene therapy for glaucoma: the dream that has not come true yet.Neural regeneration research · 2024Review
- NRF2/ARE mediated antioxidant response to glaucoma: role of glia and retinal ganglion cells.Acta neuropathologica communications · 2023Article
- Intraocular Sustained Release of EPO-R76E Mitigates Glaucoma Pathogenesis by Activating the NRF2/ARE Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Erythropoietin in Glaucoma: From Mechanism to Therapy.International journal of molecular sciences · 2023Review
- The Latest Evidence of Erythropoietin in the Treatment of Glaucoma.International journal of molecular sciences · 2022Review
- The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration.Journal of neuroinflammation · 2022Article
- A novel viewpoint in glaucoma therapeutics: enriched environment.Neural regeneration research · 2022Review
- Retinal oxidative stress activates the NRF2/ARE pathway: An early endogenous protective response to ocular hypertension.Redox biology · 2021Article
- Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium.Antioxidants (Basel, Switzerland) · 2021Article
- Use of Gene Therapy in Retinal Ganglion Cell Neuroprotection: Current Concepts and Future Directions.Biomolecules · 2021Review
- Looking into the future: Gene and cell therapies for glaucoma.Veterinary ophthalmology · 2021Review
- Microsphere antioxidant and sustained erythropoietin-R76E release functions cooperate to reduce traumatic optic neuropathy.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlaucoma is a complex neurodegeneration and a leading cause of blindness worldwide. Current therapeutic strategies, which are all directed towards lowering the intraocular pressure (IOP), do not stop progression of the disease. We have demonstrated that recombinant adeno-associated virus (rAAV) gene delivery of a form of erythropoietin with attenuated erythropoietic activity (EpoR76E) can preserve retinal ganglion cells, their axons, and vision without decreasing IOP. The goal of this study was to determine if modulation of neuroinflammation or oxidative stress played a role in the neuroprotective activity of EPO.R76E.
methodsFive-month-old DBA/2J mice were treated with either rAAV.EpoR76E or a control vector and collected at 8 months of age. Neuroprotection was assessed by quantification of axon transport and visual evoked potentials. Microglia number and morphology and cytokine and chemokine levels were quantified. Message levels of oxidative stress-related proteins were assessed.
resultsAxon transport and visual evoked potentials were preserved in rAAV.EpoR76E-treated mice. The number of microglia was decreased in retinas from 8-month-old rAAV.EpoR76E-treated mice, but proliferation was unaffected. The blood-retina barrier was also unaffected by treatment. Levels of some pro-inflammatory cytokines were decreased in retinas from rAAV.EpoR76E-treated mice including IL-1, IL-12, IL-13, IL-17, CCL4, and CCL5. TNFα messenger RNA (mRNA) was increased in retinas from 8-month-old mice compared to 3-month-old controls regardless of treatment. Expression of several antioxidant proteins was increased in retinas of rAAV.EpoR76E-treated 8-month-old mice.
conclusionsTreatment with rAAV.EpoR76E preserves vision in the DBA/2J model of glaucoma at least in part by decreasing infiltration of peripheral immune cells, modulating microglial reactivity, and decreasing oxidative stress.
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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.