ArticleInvestigative ophthalmology & visual science2015
Rat, mouse, and primate models of chronic glaucoma show sustained elevation of extracellular ATP and altered purinergic signaling in the posterior eye.
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 40 papers.
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40 citing papers in PubMed, 76 citations in OpenAlex.
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- Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.The journal of pain · 2024Article
- Role of Oxysterols in Ocular Degeneration Mechanisms and Involvement of P2X7 Receptor.Advances in experimental medicine and biology · 2024Article
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- ATP-P2XJournal of neuroinflammation · 2023Article
- Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.Frontiers in molecular neuroscience · 2023Review
- Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets.Progress in retinal and eye research · 2022Review
- CD73 controls ocular adenosine levels and protects retina from light-induced phototoxicity.Cellular and molecular life sciences : CMLS · 2022Article
- Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.Investigative ophthalmology & visual science · 2022Review
- Rapid morphologic changes to microglial cells and upregulation of mixed microglial activation state markers induced by P2X7 receptor stimulation and increased intraocular pressure.Journal of neuroinflammation · 2021Article
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- Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout.Scientific reports · 2021Article
- Adenosine receptors as promising targets for the management of ocular diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Review
- Crosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration.Frontiers in pharmacology · 2021Review
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeThe cellular mechanisms linking elevated IOP with glaucomatous damage remain unresolved. Mechanical strains and short-term increases in IOP can trigger ATP release from retinal neurons and astrocytes, but the response to chronic IOP elevation is unknown. As excess extracellular ATP can increase inflammation and damage neurons, we asked if sustained IOP elevation was associated with a sustained increase in extracellular ATP in the posterior eye.
methodsNo ideal animal model of chronic glaucoma exists, so three different models were used. Tg-Myoc(Y437H) mice were examined at 40 weeks, while IOP was elevated in rats following injection of hypertonic saline into episcleral veins and in cynomolgus monkeys by laser photocoagulation of the trabecular meshwork. The ATP levels were measured using the luciferin-luciferase assay while levels of NTPDase1 were assessed using qPCR, immunoblots, and immunohistochemistry.
resultsThe ATP levels were elevated in the vitreal humor of rats, mice, and primates after a sustained period of IOP elevation. The ecto-ATPase NTPDase1 was elevated in optic nerve head astrocytes exposed to extracellular ATP for an extended period. NTPDase1 was also elevated in the retinal tissue of rats, mice, and primates, and in the optic nerve of rats, with chronic elevation in IOP.
conclusionsA sustained elevation in extracellular ATP, and upregulation of NTPDase1, occurs in the posterior eye of rat, mouse, and primate models of chronic glaucoma. This suggests the elevation in extracellular ATP may be sustained in chronic glaucoma, and implies a role for altered purinergic signaling in the disease.
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