FIGURE 1.

Aerobic glycolysis in photoreceptor functions. Photoreceptors are post-mitotic cells, interdigitated with retinal pigment epithelium (RPE). Glucose enters the RPE through choroidal circulation. Bruch’s membrane (BM) separates the RPE and choroid. Glucose from the RPE is transported to a photoreceptor through glucose transporter 1 (Glut1). In photoreceptor cells, the majority of glucose is redirected to anabolic processes. Every day by the onset of light, 10% of photoreceptor tips are phagocytosed by the RPE, and some of the digested lipids are recycled back to photoreceptor cells. A high rate of membrane synthesis takes place in photoreceptor cells. The redirected glucose is utilized for the anabolic processes, which include lipid synthesis, RNA/DNA synthesis, and protein synthesis. The NADPH generated through the pentose phosphate pathway (PPP) is used for lipid synthesis and reduction of all-trans-retinal to all-trans-retinol by the retinol dehydrogenase 8 (RDH8). NADPH is also needed for antioxidant metabolism. Photoreceptor cells express predominantly PKM2, while PKM1 is a minor protein. Pyruvate formed during glycolysis will be converted to lactate by lactate dehydrogenase (LDH). Lactate is transported to RPE through lactate transporters (monocarboxylate transporter), where it converts to pyruvate through LDH to fuel mitochondria. Glucose-mediated oxidative phosphorylation is minimal. PKM2 favors aerobic glycolysis and has a lower affinity for PEP, which results in the accumulation of PEP in the outer segments, which triggers the PPP. BM, Bruch’s membrane; RPE, retinal pigment epithelium; OS, outer segment; IS, inner segment; RDH8, retinal dehydrogenase 8; PEP, phosphoenolpyruvate; LDH, lactate dehydrogenase; PKM1, M1 isoform of pyruvate kinase; PKM2, M2 isoform of pyruvate kinase; Glut1, glucose transporter 1; MCT, monocarboxylate transporter.