Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease

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, Jens Ulrik Lütken

AU - Hasan-Olive, Md Mahdi

AU - Diget, Elisabeth Holm

AU - Vohra, Rupali

AU - Gurubaran, Iswariyaraja Sridevi

AU - Gjedde, Albert

AU - Mariga, Shelton Tendai

AU - Skytt, Dorte M

AU - Utheim, Tor Paaske

AU - Storm-Mathisen, Jon

AU - Bergersen, Linda H

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.

U2 - 10.1007/s11064-015-1792-x

DO - 10.1007/s11064-015-1792-x

M3 - Journal article

C2 - 26677077

SN - 0364-3190

VL - 41

SP - 1229

EP - 1236

JO - Neurochemical Research

JF - Neurochemical Research

IS - 6

ER -