ArticleNature communications2020
ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 92 citations in OpenAlex.
- Transcriptomic Atlas of Human Trabecular Meshwork Uncovers the Cellular Landscape and Provides Insights into Glaucoma Pathophysiology.Research square · 2026Article
- Deficient autophagy in retinal ganglion cells impairs the degradation of intracellular organelles, leading to neurodegeneration.Cell death & disease · 2026Article
- Pharmacological restoration of impaired autophagy in retinal ganglion cells prevents abnormal mitochondrial accumulation and glaucomatous neurodegeneration.Molecular neurodegeneration · 2026Article
- Macrophage Migration Inhibitory Factor (MIF)-CD74 Signaling Pathway Mediates Trabecular Meshwork Dysfunction in Glaucoma.bioRxiv : the preprint server for biology · 2026Article
- Role of Activating Transcription Factor 4 in Metabolic, Neurologic, and Ocular Diseases.Cells · 2026Review
- CREB3L1 Modulates Extracellular Matrix Gene Expression and Proliferation in Glaucomatous Lamina Cribrosa Cells.Biomedicines · 2026Article
- Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling.Stem cells (Dayton, Ohio) · 2026Article
- Lipid-nanoparticle-mediated base editing of the trabecular meshwork rescues glaucoma in vivo.JCI insight · 2026Article
- ATF4 regulates mitochondrial dysfunction and mitophagy, contributing to corneal endothelial apoptosis.Scientific reports · 2026Article
- Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Therapeutic mRNA delivery of CRISPR-Cas9 to the trabecular meshwork reverses ocular hypertension in myocilin glaucoma.Molecular therapy. Methods & clinical development · 2025Article
- Matrine Reduces Intraocular Pressure in Corticosteroid-Induced Ocular Hypertensive Mouse Eyes.Investigative ophthalmology & visual science · 2025Article
- Protective mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells in bronchopulmonary dysplasia.Physiological research · 2025Article
- Endoplasmic Reticulum Stress Drives Neuroinflammation Through Lipocalin 2 Upregulation in Retinal Microglia After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Metabolomic Profiling of Aqueous Humor From Glaucoma Patients Identifies Metabolites With Anti-Inflammatory and Neuroprotective Potential in Mice.Investigative ophthalmology & visual science · 2025Article
- Effects of Brimonidine, Latanoprost, and Omidenepag on Tunicamycin-Induced Endoplasmic Reticulum Stress and Fibrosis in Human Trabecular Meshwork Cells.Biomolecules · 2025Article
- C/EBP Homologous Protein Expression in Retinal Ganglion Cells Induces Neurodegeneration in Mice.International journal of molecular sciences · 2025Article
- A lead role for a "secondary" axonal injury response.Neural regeneration research · 2025Article
- Impaired axonal transport contributes to neurodegeneration in a Cre-inducible mouse model of myocilin-associated glaucoma.JCI insight · 2025Article
- Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The underlying pathological mechanisms of glaucomatous trabecular meshwork (TM) damage and elevation of intraocular pressure (IOP) are poorly understood. Here, we report that the chronic endoplasmic reticulum (ER) stress-induced ATF4-CHOP-GADD34 pathway is activated in TM of human and mouse glaucoma. Expression of ATF4 in TM promotes aberrant protein synthesis and ER client protein load, leading to TM dysfunction and cell death. These events lead to IOP elevation and glaucomatous neurodegeneration. ATF4 interacts with CHOP and this interaction is essential for IOP elevation. Notably, genetic depletion or pharmacological inhibition of ATF4-CHOP-GADD34 pathway prevents TM cell death and rescues mouse models of glaucoma by reducing protein synthesis and ER client protein load in TM cells. Importantly, glaucomatous TM cells exhibit significantly increased protein synthesis along with induction of ATF4-CHOP-GADD34 pathway. These studies indicate a pathological role of ATF4-CHOP-GADD34 pathway in glaucoma and provide a possible treatment for glaucoma by targeting this pathway.
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