ArticleInvestigative ophthalmology & visual science2015
Decreased Energy Capacity and Increased Autophagic Activity in Optic Nerve Axons With Defective Anterograde Transport.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
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- Ocular Hypertension Results in Hypoxia within Glia and Neurons throughout the Visual Projection.Antioxidants (Basel, Switzerland) · 2022Article
- The Role of Axonal Transport in Glaucoma.International journal of molecular sciences · 2022Review
- Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets.Progress in retinal and eye research · 2022Review
- Degeneration of retina-brain components and connections in glaucoma: Disease causation and treatment options for eyesight preservation.Current research in neurobiology · 2022Review
- Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma.Antioxidants & redox signaling · 2021Article
- Adaptive responses to neurodegenerative stress in glaucoma.Progress in retinal and eye research · 2021Review
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- Crosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration.Frontiers in pharmacology · 2021Review
- Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies.Frontiers in pharmacology · 2021Review
- Effect of Ubiquinol on Glaucomatous Neurodegeneration and Oxidative Stress: Studies for Retinal Ganglion Cell Survival and/or Visual Function.Antioxidants (Basel, Switzerland) · 2020Article
- A broad perspective on the molecular regulation of retinal ganglion cell degeneration in glaucoma.Progress in brain research · 2020Review
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeAutophagy is a critical process, compromised in neurodegenerative disease, by which terminally differentiated cells like neurons manage cytoskeletal and organelle turnover. How autophagy relates to associated neurodegenerative pathologies remain unclear. We examined autophagy in optic neuropathy by investigating cytoskeletal degradation, mitochondria, and autophagic vesicles in the DBA2/J mouse model of glaucoma exhibiting differing levels of axon transport functionality.
methodsDBA/2J and DBA/2J(wt-gpnmb) control mice 11 to 14 months of age were injected with cholera toxin-B (CTB) to assay anterograde axonal transport. Axonal mitochondria and autophagic vesicles were analyzed with respect to transport integrity in proximal and distal optic nerve using serial block face scanning electron microscopy (3D EM).
resultsSeveral indices varied significantly between the DBA/2J and DBA/2J(wt-gpnmb) mice, including mitochondrial volume, average number of autophagic vesicles per axon, and mitochondrial cristae. However, there were no differences in mitochondrial cristae for axons with functional versus dysfunctional CTB transport, suggesting that mitochondrial dysfunction precedes overt transport blockade. Anterograde transport failure was accompanied by a dissociation of the relationship between mitochondrial and axon volumes. Autophagic vesicle profiles were significantly increased in optic nerve with transport deficit, consistent with greater autophagic activity. Mitochondria within autophagosomes, indicative of mitophagy, were observed in both proximal and distal axons.
conclusionsLoss of anterograde transport in DBA/2J optic nerve is concomitant with diminished mitochondrial volume, increased cytoskeletal breakdown and autophagic activity, and accumulation of autophagic profiles, including signs of mitophagy, in proximal optic nerve. Axons with transport deficit are metabolically underserved, though not necessarily from mitophagy.
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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.