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Abstract #106276 Published in IGR 23-3
Ocular P2 receptors and glaucoma
Shinozaki Y; Saito K; Kashiwagi K; Koizumi SNeuropharmacology 2023; 222: 109302
Adenosine triphosphate (ATP), an energy source currency in cells, is released or leaked to the extracellular space under both physiological and pathological conditions. Extracellular ATP functions as an intercellular signaling molecule through activation of purinergic P2 receptors. Ocular tissue and cells release ATP in response to physiological stimuli such as intraocular pressure (IOP), and P2 receptor activation regulates IOP elevation or reduction. Dysregulated purinergic signaling may cause abnormally elevated IOP, which is one of the major risk factors for glaucoma. Glaucoma, a leading cause of blindness worldwide, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs), which are essential retinal neurons that transduce visual information to the brain. An elevation in IOP may stress RGCs and increase the risk for glaucoma pathogenesis. In the aqueous humor of human patients with glaucoma, the ATP level is significantly elevated. Such excess amount of ATP may directly cause RGC death via a specific subtype of P2 receptors. Dysregulated purinergic signaling may also trigger inflammation, oxidative stress, and excitotoxicity via activating non-neuronal cell types such as glial cells. In this review, we discussed the physiological roles of extracellular nucleotides in the ocular tissue and their potential role in the pathogenesis of glaucoma. This article is part of the Special Issue on 'Purinergic Signaling: 50 years'.
Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan; Interdisciplinary Brain-Immune Research Center, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.
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