ArticleRedox biology2021
Retinal oxidative stress activates the NRF2/ARE pathway: An early endogenous protective response to ocular hypertension.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- The Eye as a Window to Neurodegeneration: Oxidative Stress, Optic Nerve Vulnerability, and Retinal Biomarkers-A Scoping Review.Antioxidants (Basel, Switzerland) · 2026Review
- An ROS-responsive, RGC-targeted nanotherapeutic strategy with a TRPV4 antagonist restores autophagic flux and protects RGCs in a rat model of chronic ocular hypertension.Journal of nanobiotechnology · 2026Article
- Oxidative Stress in Glaucoma: From Pathogenic Mechanisms to Emerging Antioxidant Therapies.Antioxidants (Basel, Switzerland) · 2026Review
- Pathophysiological Roles of Oxidative Stress and the Translational Potential of Antioxidant Therapy in Retinal Vein Occlusion.Antioxidants (Basel, Switzerland) · 2026Review
- Experimental models to study oxidative stress in glaucoma: integratingFrontiers in pharmacology · 2026Review
- Changes in the Protein Composition of the Aqueous Humor in Patients with Glaucoma: An Update Review.International journal of molecular sciences · 2025Review
- Gene and phenome-based analysis of the shared genetic architecture of eye diseases.American journal of human genetics · 2025Article
- Article
- Emerging strategies targeting genes and cells in glaucoma.Vision research · 2025Review
- Role of reactive oxygen species and oxidative stress in the pathomechanism of glaucoma.Medical hypothesis, discovery & innovation ophthalmology journal · 2025Review
- Serum Oxidative Stress-related Biomarkers in Ocular Hypertension and Glaucoma.Journal of ophthalmic & vision research · 2024Article
- Article
- The Identification of New Pharmacological Targets for the Treatment of Glaucoma: A Network Pharmacology Approach.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Alleviating Effect of Lipid Phytochemicals in Seed Oil (Nutrients · 2024Article
- Photocrosslinkable Sericin Hydrogel Injected into the Anterior Chamber of Mice with Chronic Ocular Hypertension Efficacy, Medication Sensitivity, and Material Safety.Bioengineering (Basel, Switzerland) · 2024Article
- The PI3K/Akt-Nrf2 Signaling Pathway and Mitophagy Synergistically Mediate Hydroxytyrosol to Alleviate Intestinal Oxidative Damage.International journal of biological sciences · 2024Article
- The concept of gene therapy for glaucoma: the dream that has not come true yet.Neural regeneration research · 2024Review
- Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.International journal of nanomedicine · 2024Article
- Molecular pathways in experimental glaucoma models.Frontiers in neuroscience · 2024Review
- Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management.PloS one · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidative stress contributes to degeneration of retinal ganglion cells and their axons in glaucoma, a leading cause of irreversible blindness worldwide, through sensitivity to intraocular pressure (IOP). Here, we investigated early elevations in reactive oxygen species (ROS) and a role for the NRF2-KEAP1-ARE endogenous antioxidant response pathway using microbead occlusion to elevate IOP in mice. ROS levels peaked in the retina at 1- and 2-wks following IOP elevation and remained elevated out to 5-wks. Phosphorylation of NRF2 and antioxidant gene transcription and protein levels increased concomitantly at 2-wks after IOP elevation, along with phosphorylation of PI3K and AKT. Inhibiting PI3K or AKT signaling prevented NRF2 phosphorylation and reduced transcription of antioxidant-regulated genes. Ocular hypertensive mice lacking Nrf2 had elevated ROS and a diminished increase in antioxidant gene expression. They also exhibited earlier axon degeneration and loss of visual function. In conclusion, the NRF2-KEAP1-ARE pathway is endogenously activated early in ocular hypertension due to phosphorylation of NRF2 by the PI3K/AKT pathway and serves to slow the onset of axon degeneration and vision loss in glaucoma. These data suggest that exogenous activation of this pathway might further slow glaucomatous neurodegeneration.
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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 Socratic graph.