title: Ocular Purine Receptors as Drug Targets in the Eye.
abstract: Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A1, A2A, and A3. An A1AR agonist is in clinical trials for glaucoma, A2AAR reduces neuroinflammation, A3AR protects retinal ganglion cells from apoptosis, and both A3AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y2and P2Y6, lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases.
authors: 1 Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland.
authors: Kenneth A
authors: KA
authors: Jacobson
authors: 2 Departments of Physiology and Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania.
authors: Mortimer M
authors: MM
authors: Civan
mesh_terms: D000322:Adrenergic Agonists / Q000737:chemistry / Q000494:pharmacology*; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011983:Receptors, Purinergic / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000322:Adrenergic Agonists; D008024:Ligands; D011983:Receptors, Purinergic
keywords: ATP; P2X receptor; P2Y receptor; adenosine receptor