title: Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.
abstract: In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark. mkolko@dadlnet.dk.|Department of Ophthalmology, Roskilde Hospital, Roskilde, Denmark. mkolko@dadlnet.dk.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kolko
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Fia
authors.initials: F
authors.lastname: Vosborg
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Ulrik L
authors.initials: UL
authors.lastname: Henriksen
authors.affiliation: Synaptic Neurochemistry Laboratory, Division of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|Brain and Muscle Energy Group, Faculty of Dentistry, Institute of Oral Biology, University of Oslo, PO Box 1152, Blindern, 0316, Oslo, Norway.
authors.forename: Md Mahdi
authors.initials: MM
authors.lastname: Hasan-Olive
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.|Brain and Muscle Energy Group, Faculty of Dentistry, Institute of Oral Biology, University of Oslo, PO Box 1152, Blindern, 0316, Oslo, Norway.
authors.forename: Elisabeth Holm
authors.initials: EH
authors.lastname: Diget
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Rupali
authors.initials: R
authors.lastname: Vohra
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Iswariya Raja Sridevi
authors.initials: IR
authors.lastname: Gurubaran
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.|Synaptic Neurochemistry Laboratory, Division of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|Brain and Muscle Energy Group, Faculty of Dentistry, Institute of Oral Biology, University of Oslo, PO Box 1152, Blindern, 0316, Oslo, Norway.
authors.forename: Shelton Tendai
authors.initials: ST
authors.lastname: Mariga
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
authors.forename: Dorte M
authors.initials: DM
authors.lastname: Skytt
authors.affiliation: Brain and Muscle Energy Group, Faculty of Dentistry, Institute of Oral Biology, University of Oslo, PO Box 1152, Blindern, 0316, Oslo, Norway.|Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Tor Paaske
authors.initials: TP
authors.lastname: Utheim
authors.affiliation: Synaptic Neurochemistry Laboratory, Division of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Storm-Mathisen
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, and Center for Healthy Aging, University of Copenhagen, The Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark. l.h.bergersen@medisin.uio.no.|Brain and Muscle Energy Group, Faculty of Dentistry, Institute of Oral Biology, University of Oslo, PO Box 1152, Blindern, 0316, Oslo, Norway. l.h.bergersen@medisin.uio.no.
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
mesh_terms: D000818:Animals; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D012160:Retina / Q000473:pathology / Q000502:physiology*; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D027501:Monocarboxylic Acid Transporters; D019344:Lactic Acid
keywords: Diabetes retinopathy; Energy metabolism; Glaucoma; Lactate receptor; Lactate transport; Retina; Transmitter