ArticleScientific reports2023
Long-term HIF-1α stabilization reduces respiration, promotes mitophagy, and results in retinal cell death.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Physiological Hypoxia and Pharmacological HIF Stabilization Induce Distinct but Overlapping Responses in Retinal Pigment Epithelial Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Extrinsic Regulation of Optic Nerve Axon Regeneration in the Adult Central Nervous System.Cells · 2026Review
- Neutrophil extracellular traps in osteoporosis: mechanistic links to bone remodeling imbalance and therapeutic perspectives.Molecular biology reports · 2026Review
- Review
- Hypoxia, ROS, and HIF Signaling in I/R Injury: Implications and Future Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Intratumoral microbiota: bidirectional modulation of tumor radiosensitivity.Frontiers in immunology · 2026Review
- Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer.Cancer letters · 2025Article
- HIF1 activity in photoreceptors drives type 3 neovascularization and retinal atrophy in a new mouse model of age-related macular degeneration.Cell death & disease · 2025Article
- Correlation of autoantibody profiles with clinical parameters in exfoliative glaucoma patients.International ophthalmology · 2025Article
- Compression injury regulates astrocyte morphology, metabolic function, and extracellular matrix modification in a 3D hydrogel.bioRxiv : the preprint server for biology · 2025Article
- Protocol for the purification and culture of primary retinal ganglion cells and development of common pathological models.Journal of molecular histology · 2025Article
- Article
- Identification of diagnostic biomarkers and dissecting immune microenvironment with crosstalk genes in the POAG and COVID-19 nexus.Scientific reports · 2025Article
- Hypoxia and growth factor profiling in high myopia: linking HIF-1α suppression and PDGF-BB activation to structural degeneration.Frontiers in medicine · 2025Article
- The Identification of New Pharmacological Targets for the Treatment of Glaucoma: A Network Pharmacology Approach.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Ocular Inflammation and Oxidative Stress as a Result of Chronic Intermittent Hypoxia: A Rat Model of Sleep Apnea.Antioxidants (Basel, Switzerland) · 2024Article
- The ketogenic diet and hypoxia promote mitophagy in the context of glaucoma.Frontiers in cellular neuroscience · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test whether chronic HIF activation and the attendant metabolic reprogramming can initiate glaucoma-associated pathology independently of ocular hypertension. HIF-1α stabilization was induced in mice for 2 and 4 weeks by inhibiting prolyl hydroxylases using the small molecule Roxadustat. HIF-1α stabilization and the expression of its downstream bioenergetic targets were investigated in the retina by immunofluorescence, capillary electrophoresis, and biochemical enzyme activity assays. Roxadustat dosing resulted in significant stabilization of HIF-1α in the retina by 4 weeks, and upregulation in glycolysis-associated proteins (GLUT3, PDK-1) and enzyme activity in both neurons and glia. Accordingly, succinate dehydrogenase, mitochondrial marker MTCO1, and citrate synthase activity were significantly decreased at 4 weeks, while mitophagy was significantly increased. TUNEL assay showed significant apoptosis of cells in the retina, and PERG amplitude was significantly decreased with 4 weeks of HIF-1α stabilization. A significant increase in AMPK activation and glial hypertrophy, concomitant with decreases in retinal ganglion cell function and inner retina cell death suggests that chronic HIF-1α stabilization alone is detrimental to retina metabolic homeostasis and cellular survival.
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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.