ArticleMolecular neurodegeneration2018
Targeting Hif1a rescues cone degeneration and prevents subretinal neovascularization in a model of chronic hypoxia.
Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 42 citations in OpenAlex.
- Age-Related Neurovascular Dysfunction in the Retina and Potential Pathogenic Mechanisms.Investigative ophthalmology & visual science · 2026Review
- RNA interference to reduceMolecular vision · 2026Article
- Unravelling the Mechanism of N-Acetylcysteine in Alleviating Smoke-Induced Hypoxia-Driven Ocular Defects in Drosophila melanogaster.Molecular neurobiology · 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
- Targeting hypoxia-inducible factor-1 in a hypoxidative stress model protects retinal pigment epithelium cells from cell death and metabolic dysregulation.Cell death discovery · 2025Article
- Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.Redox biology · 2025Article
- Preclinical Retinal Disease Models: Applications in Drug Development and Translational Research.Pharmaceuticals (Basel, Switzerland) · 2025Review
- CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa.Cell reports. Medicine · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Method to Regulate Monocyte Function by Silencing HIF-1α mRNA in a Model of Retinal Neovascularization.ACS applied nano materials · 2023Article
- Cigarette smoke causes a bioenergetic crisis in RPE cells involving the downregulation of HIF-1α under normoxia.Cell death discovery · 2023Article
- Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.Frontiers in molecular neuroscience · 2023Review
- Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction.Cell death & disease · 2022Article
- A Novel Hypoxia-inducible Factor 1α Inhibitor KC7F2 Attenuates Oxygen-induced Retinal Neovascularization.Investigative ophthalmology & visual science · 2022Article
- Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones.BMC biology · 2022Article
- DIX domain containing 1 (DIXDC1) modulates VEGFR2 level in vasculatures to regulate embryonic and postnatal retina angiogenesis.BMC biology · 2022Article
- Electrophysiological mechanisms underlying hypoxia-induced deficits in visual spatial and non-spatial discrimination.Physiological reports · 2021Article
- Transcriptomic analysis of the mouse retina after acute and chronic normobaric and hypobaric hypoxia.Scientific reports · 2021Article
- Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization.Frontiers in neuroscience · 2021Review
- APE1/Ref-1 as a Novel Target for Retinal Diseases.Journal of cellular signaling · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDegeneration of cone photoreceptors leads to loss of vision in patients suffering from age-related macular degeneration (AMD) and other cone dystrophies. Evidence, such as choroidal ischemia and decreased choroidal blood flow, implicates reduced tissue oxygenation in AMD pathology and suggests a role of the cellular response to hypoxia in disease onset and progression. Such a chronic hypoxic situation may promote several cellular responses including stabilization of hypoxia-inducible factors (HIFs).
methodsTo investigate the consequence of a chronic activation of the molecular response to hypoxia in cones, von Hippel Lindau protein (VHL) was specifically ablated in cones of the all-cone R91W;Nrl
resultsCone-specific ablation of Vhl resulted in stabilization and activation of hypoxia-inducible factor 1A (HIF1A) which led to increased expression of genes associated with hypoxia and retinal stress. Our data demonstrate severe cone degeneration and pathologic vessel growth, features that are central to AMD pathology. Subretinal neovascularization was accompanied by vascular leakage and infiltration of microglia cells. Interestingly, we observed increased expression of tissue inhibitor of metalloproteinase 3 (Timp3) during the aging process, a gene associated with AMD and Bruch's membrane integrity. Additional deletion of Hif1a protected cone cells, prevented pathological vessel growth and preserved vision.
conclusionsOur data provide evidence for a HIF1A-mediated mechanism leading to pathological vessel growth and cone degeneration in response to a chronic hypoxia-like situation. Consequently, our results identify HIF1A as a potential therapeutic target to rescue hypoxia-related vision loss in patients.
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