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.
Diseases of the optic nerve head involving changes in blood flow are common. However, the pathophysiology is not always fully understood. Several non-invasive methods for measuring optic nerve head blood flow are available, but currently no gold standard has been established. Methods for measuring blood flow in optic neuropathies including colour Doppler imaging, retinal function imager, optical coherence tomography angiography and laser speckle flowgraphy are reviewed. Ultrasound colour Doppler imaging is a fast measurement technique where several different parameters, especially the blood flow velocity, can be calculated. Though used for many years in ophthalmology, its use is not standardized and it requires significant observer skills. The retinal function imager is a direct method where the haemoglobin in erythrocytes is visualized and blood flow velocities in retinal vessels are calculated from a series of photos. The technique is not suitable for direct measurement of blood flow within the optic nerve head. Laser speckle flowgraphy uses a laser light which creates a light scatter pattern in the tissue. Particles moving in the area causes changes in the speckle pattern from which a relative blood flow can be estimated. It is, however, not known whether optic nerve head microcirculation is measurable with the technique. Optical coherence tomography angiography uses multiple scans to evaluate blood flow with good reproducibility but often problems with artefacts. The technique is continuously being refined and increasingly used in research as a tool for the study of blood flow in retinopathies and optic neuropathies. Most of the conducted studies are based on small sample sizes, but some of the methods show promising results in an optic nerve head blood flow research setting. Further and larger studies are required to provide standardized and comparable measurements before one or more of the methods can be considered clinical helpful in daily practice.
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