title: Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland.
abstract: This review highlights recent findings that describ how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca(2+) concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target may be a key issue in understanding how physiological signaling becomes pathological in ocular disease.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Sanderson
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Dartt
authors.affiliation: Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Vickery
authors.initials: V
authors.lastname: Trinkaus-Randall
authors.affiliation: Department of Biochemistry, Faculty of Optometry, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pintor
authors.affiliation: Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Mortimer M
authors.initials: MM
authors.lastname: Civan
authors.affiliation: Department of Physiology, University of Arizona, Tucson, AZ, USA; Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Delamere
authors.affiliation: Department of Anatomy and of Neuroscience, University of Melbourne, Victoria, Australia.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Fletcher
authors.affiliation: Department of Visual Neuroscience, UCL Institute of Ophthalmology, London, UK.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Salt
authors.affiliation: Institute of Human Genetics, Franz-Josef-Strauß-Allee, Regensburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Grosche
authors.affiliation: Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: chm@exchange.upenn.edu.
authors.forename: Claire H
authors.initials: CH
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D063928:Ependymoglial Cells / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000378:metabolism*; D005128:Eye Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007765:Lacrimal Apparatus / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism; D011684:Purine Nucleosides / Q000502:physiology*; D011685:Purine Nucleotides / Q000502:physiology*; D055351:Retinal Neurons / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014129:Trabecular Meshwork / Q000378:metabolism
chemical_list: D011684:Purine Nucleosides; D011685:Purine Nucleotides
keywords: ATP; P2X; P2Y; RPE; adenosine; cornea; diadenosine polyphosphates; eye; lacrimal gland; lens; neurotransmitter; retina; trabecular meshwork