ArticleCell death discovery2021
The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Post-translational modifications of selective autophagy receptors: orchestrating cellular homeostasis, disease pathogenesis, and therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- Chitosan-rapamycin carbon dots rejuvenate autologous Sca-1⁺ stem cells paracrine function for neuroprotection in normal tension glaucoma.Stem cell research & therapy · 2026Article
- Reversing Mitochondrial Dysfunction in Optineurin E50K Glaucoma: A Metabolic Approach to Neuroprotection.Research square · 2026Article
- Experimental models to study oxidative stress in glaucoma: integratingFrontiers in pharmacology · 2026Review
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Single-Cell Transcriptome Analysis of the Retina During the Development of Normal Tension Glaucoma in Mice.Inflammation · 2025Article
- Microglia Drive Peripapillary Vascular Density Reduction in Normal Tension Glaucoma by Regulating the Rpl17/Stat5b/Apoa1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inhibiting NLRP3 Inflammasome Activation to Alleviate Retinal Inflammation and Protect the Optic Nerve of OPTN(E50K)Mice.Inflammation · 2025Article
- Non-human primates as preclinical models for optic nerve research: advancing insights into their application and potential.Eye (London, England) · 2025Review
- Emerging strategies targeting genes and cells in glaucoma.Vision research · 2025Review
- Revealing the role of regulatory microglial IRF7-NLRP3 interactions in optic nerve damage of normal-tension glaucoma based on single-cell RNA sequencing.Frontiers in immunology · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- TDP-43 as a potential retinal biomarker for neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025Review
- Age-related effects of optineurin deficiency in the mouse eye.Vision research · 2024Article
- Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.Acta neuropathologica communications · 2024Article
- Normal-Tension Glaucoma and Potential Clinical Links to Alzheimer's Disease.Journal of clinical medicine · 2024Review
- Identification ofGenetics in medicine open · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The glaucoma-associated E50K mutation in optineurin (OPTN) is known to affect autophagy and cause the apoptosis of retinal ganglion cells (RGCs), but the pathogenic mechanism remains unclear. In this study, we investigated whether the OPTN (E50K) mutation caused TDP-43 aggregation by disrupting autophagy in vivo and in vitro. OPTN (E50K) mutant mice were generated and analysed for genotype and phenotype. Adeno-associated virus type 2 vectors containing either GFP only, GFP-tagged wild-type OPTN or GFP-tagged E50K-mutated OPTN were used to transfect R28 cells. Loss of RGCs decreased retinal thickness and visual impairment were observed in OPTN (E50K) mice compared with WT mice. Moreover, overexpression of E50K OPTN induced R28 cell apoptosis. Increased p62/SQSTM1 and LC3-II levels indicated that autophagic flux was inhibited and contributed to TDP-43 aggregation in vivo and in vitro. We found that rapamycin effectively reduced the aggregation of TDP-43 in OPTN (E50K) mice and decreased the protein levels of p62/SQSTM1 and the autophagic marker LC3-II. Moreover, rapamycin increased the RGC number and visual function of E50K mice. In addition, we also observed increased cytoplasmic TDP-43 in the spinal cord and motor dysfunction in 24-month-old OPTN (E50K) mice, indicating that TDP-43 accumulation may be the common pathological mechanism of glaucoma and amyotrophic lateral sclerosis (ALS). In conclusion, the disruption of autophagy by OPTN (E50K) affected the degradation of TDP-43 and may play an important role in OPTN (E50K)-mediated glaucomatous retinal neurodegeneration.
Identifiers
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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.