TY - JOUR
T1 - Lactate Transport and Receptor Actions in Retina
T2 - Potential Roles in Retinal Function and Disease
AU - Kolko, Miriam
AU - Vosborg, Fia
AU - Henriksen, Ulrik L.
AU - Hasan-Olive, Md Mahdi
AU - Diget, Elisabeth Holm
AU - Vohra, Rupali
AU - Gurubaran, Iswariya Raja Sridevi
AU - Gjedde, Albert
AU - Mariga, Shelton Tendai
AU - Skytt, Dorte M.
AU - Utheim, Tor Paaske
AU - Storm-Mathisen, Jon
AU - Bergersen, Linda H.
N1 - Funding Information:
Acknowledgments This work has been supported by grants from the University of Oslo, Anders Jahre’s Foundation for the Advancement of Science, and The Norwegian Research Council (including Unikard, a joint Research Council—Health Authority Grant), Norway, and from the University of Copenhagen, Velux Foundation, and the Lundbeck Foundation, Denmark.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Diabetes retinopathy
KW - Energy metabolism
KW - Glaucoma
KW - Lactate receptor
KW - Lactate transport
KW - Retina
KW - Transmitter
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U2 - 10.1007/s11064-015-1792-x
DO - 10.1007/s11064-015-1792-x
M3 - Article
C2 - 26677077
AN - SCOPUS:84949981048
VL - 41
SP - 1229
EP - 1236
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 6
ER -