Glucose metabolism in mammalian photoreceptor inner and outer segments

Abstract

Photoreceptors are the first-order neurons of the visual pathway, converting light into electrical signals. Rods and cones are the two main types of photoreceptors in the mammalian retina. Rods are specialized for sensitivity at the expense of resolution and are responsible for vision in dimly lit conditions. Cones are responsible for high acuity central vision and colour vision. Many human retinal diseases are characterized by a progressive loss of photoreceptors. Photoreceptors consist of four primary regions: outer segments, inner segments, cell bodies and synaptic terminals. Photoreceptors consume large amounts of energy, and therefore, energy metabolism may be a critical juncture that links photoreceptor function and survival. Cones require more energy than rods, and cone degeneration is the main cause of clinically significant vision loss in retinal diseases. Photoreceptor segments are capable of utilizing various energy substrates, including glucose, to meet their large energy demands. The pathways by which photoreceptor segments meet their energy demands remain incompletely understood. Improvements in the understanding of glucose metabolism in photoreceptor segments may provide insight into the reasons why photoreceptors degenerate due to energy failure. This may, in turn, assist in developing bio-energetic therapies aimed at protecting photoreceptors.

Rod phototransduction and light signal transmission during type 2 diabetes

“…While our experiments did not identify the mechanisms by which light-evoked photoreceptor responses are increased in the presence of additional glucose, likely targets include energy dependent processes in photoreceptors such as Na + /K + ATPases, Na + /Ca 2+ /K + exchangers and Ca 2+ ATPases (42), ATP-sensitive K + channels expressed in photoreceptors (43) or other ATP-dependent processes. The main glucose transporters expressed in photoreceptors are the insulin-independent GLUT-1 and insulin-dependent GLUT-4 (42), which have previously been reported to be reduced in diabetes (31; 44; 45), thus potentially explaining the inability of the photoreceptors in db/db mice to utilize increased glucose concentrations to promote their light responses. However, these findings are not universal and increased expression of GLUT-1 in diabetes has also been reported (39).…”

“…While photoreceptors are highly metabolically active and mostly depend on glucose as their source of energy (42), effects of acute hyperglycemia on retinal function remain unclear. Studies in patients with diabetes and diabetic animal models suggest a correlation between bipolar cell function and blood glucose levels.…”

Spectral‐domain optical coherence tomography imaging of normal foveae: A pilot study in 17 diurnal birds of prey

“…A similarly interesting finding was that the CFPD was ~30% lesser than TPFD in all species. Cone photoreceptors require more energy than rods . As the pecten appears to be associated with providing nourishment and oxygen supply to the retina and as the vitreous allows relatively molecular mobility, it is possible that the closer proximity of the central fovea to the pecten is beneficial due to the higher energy needs of the central fovea .…”

“…Cone photoreceptors require more energy than rods. 55 As the pecten appears to be associated with providing nourishment and oxygen supply to the retina and as the vitreous allows relatively molecular mobility, it is possible that the closer proximity of the central fovea to the pecten is beneficial due to the higher energy needs of the central fovea. 56 Photoreceptors and retinal pigment epithelium (RPE) are responsible for phototransduction, which require a large amount of energy; therefore, it would not be surprising if the central fovea had higher energetic requirements given its functionality and metabolic requirements.…”

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

“…Indeed, photoreceptor function is highly susceptible to glycolytic inhibition (via sodium iodoacetate injection) and mature 'RP' rats lacking a majority of their photoreceptors display an ~50% reduction in glycolytic activity compared to normal rat retinas [16,17]. In addition to meeting the high energy demands of photoreceptors, glucose metabolism plays other non-energetic roles in the retina [18,19]. For example, glucose metabolism by the pentose phosphate pathway leads to the production of intracellular glutathione, which prevents neuronal cell death through redox inactivation of cytochrome c-mediated apoptosis pathways [20].…”