ArticleExperimental eye research2016
Early astrocyte redistribution in the optic nerve precedes axonopathy in the DBA/2J mouse model of glaucoma.
Article in Experimental eye research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 95 citations in OpenAlex.
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
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- The structure, function, and distribution of gap junctions in the retina: Life cycle in health and disease.Journal of cell communication and signaling · 2025Review
- Sustained Experimental Myopia Exacerbates the Effect of Eye Growth on Retinal Ganglion Cell Density and Function.International journal of molecular sciences · 2025Article
- Astrocytes in the mouse brain respond bilaterally to unilateral retinal neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- In Search of Mouse Models for Exfoliation Syndrome.American journal of ophthalmology · 2024Article
- Acute ocular hypertension in the living human eye: Model description and initial cellular responses to elevated intraocular pressure.Vision research · 2024Article
- Enhanced Optic Nerve Expansion and Altered Ultrastructure of Elastic Fibers Induced by Lysyl Oxidase Inhibition in a Mouse Model of Marfan Syndrome.The American journal of pathology · 2024Article
- Enhanced Synaptic Inhibition in the Dorsolateral Geniculate Nucleus in a Mouse Model of Glaucoma.eNeuro · 2024Article
- Sustained Retinal Defocus Increases the Effect of Induced Myopia on the Retinal Astrocyte Template.Cells · 2024Article
- IOP and glaucoma damage: The essential role of optic nerve head and retinal mechanosensors.Progress in retinal and eye research · 2024Review
- Evaluation of the LDN-0060609 PERK Inhibitor as a Selective Treatment for Primary Open-Angle Glaucoma: An In Vitro Study on Human Retinal Astrocytes.International journal of molecular sciences · 2024Article
- Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium.Molecular neurodegeneration · 2023Review
- Autophagy deficiency protects against ocular hypertension and neurodegeneration in experimental and spontanous glaucoma mouse models.Cell death & disease · 2023Article
- Astrocytes in the Optic Nerve Are Heterogeneous in Their Reactivity to Glaucomatous Injury.Cells · 2023Article
- Erythropoietin Protects against Retinal Damage in A Rat Model of Optic Neuropathy via Glial Suppression.Cell journal · 2023Article
- Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients.Pharmaceuticals (Basel, Switzerland) · 2023Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Glaucoma challenges the survival of retinal ganglion cell axons in the optic nerve through processes dependent on both aging and ocular pressure. Relevant stressors likely include complex interplay between axons and astrocytes, both in the retina and optic nerve. In the DBA/2J mouse model of pigmentary glaucoma, early progression involves axonopathy characterized by loss of functional transport prior to outright degeneration. Here we describe novel features of early pathogenesis in the DBA/2J nerve. With age the cross-sectional area of the nerve increases; this is associated generally with diminished axon packing density and survival and increased glial coverage of the nerve. However, for nerves with the highest axon density, as the nerve expands mean cross-sectional axon area enlarges as well. This early expansion was marked by disorganized axoplasm and accumulation of hyperphosphorylated neurofilamants indicative of axonopathy. Axon expansion occurs without loss up to a critical threshold for size (about 0.45-0.50 μm(2)), above which additional expansion tightly correlates with frank loss of axons. As well, early axon expansion prior to degeneration is concurrent with decreased astrocyte ramification with redistribution of processes towards the nerve edge. As axons expand beyond the critical threshold for loss, glial area resumes an even distribution from the center to edge of the nerve. We also found that early axon expansion is accompanied by reduced numbers of mitochondria per unit area in the nerve. Finally, our data indicate that both IOP and nerve expansion are associated with axon enlargement and reduced axon density for aged nerves. Collectively, our data support the hypothesis that diminished bioenergetic resources in conjunction with early nerve and glial remodeling could be a primary inducer of progression of axon pathology in glaucoma.
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