ArticlePloS one2013
Dynamic increase in extracellular ATP accelerates photoreceptor cell apoptosis via ligation of P2RX7 in subretinal hemorrhage.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 92 citations in OpenAlex.
- Macular sub-ILM hemorrhage as a favorable prognostic factor in ruptured retinal arterial macroaneurysm.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Quantitative Markers of Neural Changes, Retinal Thickness, and Responses to Electrical Stimulation in Retinal Degeneration.Ophthalmology science · 2026Article
- P2RX7 modulates the function of human microglia-like cells and mediates the association of IL18 with Alzheimer's disease traits.Neurobiology of disease · 2025Article
- Iron: More than Meets the Eye.Nutrients · 2025Review
- Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.Purinergic signalling · 2025Article
- Isolation and Characterization of Mouse Choroidal Melanocytes and Their Proinflammatory Characteristics.Cells · 2025Article
- [Berberine Alleviates Chronic Retinal Light Damage in Mice: A Study of the Role of P2X7R and the Mechanisms Involved].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Five-year Outcome of Aflibercept Administration with "Treat and Extend" for Neovascular Age-Related Macular Degeneration.Clinical ophthalmology (Auckland, N.Z.) · 2025Article
- Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Intraocular kinetics of pathological ATP after photoreceptor damage in rhegmatogenous retinal detachment.Japanese journal of ophthalmology · 2024Article
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- Role of Oxysterols in Ocular Degeneration Mechanisms and Involvement of P2X7 Receptor.Advances in experimental medicine and biology · 2024Article
- Saffron and retinal neurodegenerative diseases: Relevance of chemical composition.Journal of anatomy · 2023Article
- P2X7 Is Involved in the Mouse Retinal Degeneration via the Coordinated Actions in Different Retinal Cell Types.Antioxidants (Basel, Switzerland) · 2023Article
- Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration.Frontiers in neuroscience · 2023Review
- Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders.International journal of molecular sciences · 2022Review
- Plasma and aqueous humor levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.International journal of ophthalmology · 2022Article
- Long-term observation of outer retinopathy-like sequelae in intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage using multimodal imaging.Advances in ophthalmology practice and research · 2021Article
- 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
- ATP and Adenosine in the Retina and Retinal Diseases.Frontiers in pharmacology · 2021Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Photoreceptor degeneration is the most critical cause of visual impairment in age-related macular degeneration (AMD). In neovascular form of AMD, severe photoreceptor loss develops with subretinal hemorrhage due to choroidal neovascularization (CNV), growth of abnormal blood vessels from choroidal circulation. However, the detailed mechanisms of this process remain elusive. Here we demonstrate that neovascular AMD with subretinal hemorrhage accompanies a significant increase in extracellular ATP, and that extracellular ATP initiates neurodegenerative processes through specific ligation of Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7; P2X7 receptor). Increased extracellular ATP levels were found in the vitreous samples of AMD patients with subretinal hemorrhage compared to control vitreous samples. Extravascular blood induced a massive release of ATP and photoreceptor cell apoptosis in co-culture with primary retinal cells. Photoreceptor cell apoptosis accompanied mitochondrial apoptotic pathways, namely activation of caspase-9 and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, as well as TUNEL-detectable DNA fragmentation. These hallmarks of photoreceptor cell apoptosis were prevented by brilliant blue G (BBG), a selective P2RX7 antagonist, which is an approved adjuvant in ocular surgery. Finally, in a mouse model of subretinal hemorrhage, photoreceptor cells degenerated through BBG-inhibitable apoptosis, suggesting that ligation of P2RX7 by extracellular ATP may accelerate photoreceptor cell apoptosis in AMD with subretinal hemorrhage. Our results indicate a novel mechanism that could involve neuronal cell death not only in AMD but also in hemorrhagic disorders in the CNS and encourage the potential application of BBG as a neuroprotective therapy.
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