. Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France.
. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Int J Mol Sci. 2019 Feb 11;20(3):762. doi: 10.3390/ijms20030762.
The retinal pigment epithelium (RPE) forms the outer blood⁻retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized via OXPHOS. Excess lactate in the RPE is transported across the basolateral membrane to the choroid. The uptake of glucose by cone photoreceptor cells is enhanced by rod-derived cone viability factor (RdCVF) secreted by rods and by insulin signaling. Together, the three cells act as symbiotes: the RPE supplies the glucose from the choroidal circulation to the photoreceptors, the rods help the cones, and both produce lactate to feed the RPE. In age-related macular degeneration this delicate ménage à trois is disturbed by the chronic infiltration of inflammatory macrophages. These immune cells also rely on aerobic glycolysis and compete for glucose and produce lactate. We here review the glucose metabolism in the homeostasis of the outer retina and in macrophages and hypothesize what happens when the metabolism of photoreceptors and the RPE is disturbed by chronic inflammation.
视网膜色素上皮（RPE）形成了外血-视网膜屏障，并通过 GLUT1 促进葡萄糖向视网膜外的跨上皮转运。在感光细胞中，葡萄糖通过三羧酸循环（TCA）和氧化磷酸化（OXPHOS）代谢，但也通过有氧糖酵解生成甘油，用于合成磷脂以更新其外节。感光细胞中的有氧糖酵解也导致大量乳酸的产生，这些乳酸通过 RPE 从视网膜下腔转运到脉络膜循环。RPE 摄取的乳酸被转化为丙酮酸，并通过 OXPHOS 进行代谢。RPE 中的过量乳酸通过基底外侧膜转运到脉络膜。杆状细胞衍生的视锥细胞生存因子（RdCVF）和胰岛素信号增强了锥状感光细胞对葡萄糖的摄取。这三种细胞共同作用，形成共生关系：RPE 从脉络膜循环中向感光细胞提供葡萄糖，杆状细胞帮助锥状细胞，同时产生乳酸来滋养 RPE。在年龄相关性黄斑变性中，这种微妙的共生关系被慢性浸润的炎症性巨噬细胞破坏。这些免疫细胞也依赖于有氧糖酵解，与葡萄糖竞争，并产生乳酸。我们在这里回顾了外视网膜和巨噬细胞中葡萄糖代谢的稳态，并假设当感光细胞和 RPE 的代谢受到慢性炎症的干扰时会发生什么。
