PMID- 38142757 OWN - NLM STAT- MEDLINE DCOM- 20240220 LR - 20240227 IS - 1879-260X (Electronic) IS - 0925-4439 (Linking) VI - 1870 IP - 3 DP - 2024 Mar TI - Glucose transport, transporters and metabolism in diabetic retinopathy. PG - 166995 LID - S0925-4439(23)00361-7 [pii] LID - 10.1016/j.bbadis.2023.166995 [doi] AB - Diabetic retinopathy (DR) is the most common reason for blindness in working-age individuals globally. Prolonged high blood glucose is a main causative factor for DR development, and glucose transport is prerequisite for the disturbances in DR caused by hyperglycemia. Glucose transport is mediated by its transporters, including the facilitated transporters (glucose transporter, GLUTs), the "active" glucose transporters (sodium-dependent glucose transporters, SGLTs), and the SLC50 family of uniporters (sugars will eventually be exported transporters, SWEETs). Glucose transport across the blood-retinal barrier (BRB) is crucial for nourishing the neuronal retina in the context of retinal physiology. This physiological process primarily relies on GLUTs and SGLTs, which mediate the glucose transportation across both the cell membrane of retinal capillary endothelial cells and the retinal pigment epithelium (RPE). Under diabetic conditions, increased accumulation of extracellular glucose enhances the retinal cellular glucose uptake and metabolism via both glycolysis and glycolytic side branches, which activates several biochemical pathways, including the protein kinase C (PKC), advanced glycation end-products (AGEs), polyol pathway and hexosamine biosynthetic pathway (HBP). These activated biochemical pathways further increase the production of reactive oxygen species (ROS), leading to oxidative stress and activation of Poly (ADP-ribose) polymerase (PARP). The activated PARP further affects all the cellular components in the retina, and finally resulting in microangiopathy, neurodegeneration and low-to-moderate grade inflammation in DR. This review aims to discuss the changes of glucose transport, glucose transporters, as well as its metabolism in DR, which influences the retinal neurovascular unit (NVU) and implies the possible therapeutic strategies for treating DR. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Zhang, Chaoyang AU - Zhang C AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: chaoyang.zhang@shgh.cn. FAU - Gu, Limin AU - Gu L AD - Department of Ophthalmology, Shanghai Aier Eye Hospital, Shanghai, China. Electronic address: gulimin@aierchina.com. FAU - Xie, Hai AU - Xie H AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: xiehai@shsdyrmyy.wecom.work. FAU - Liu, Yan AU - Liu Y AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: liuyan2@shsdyrmyy.wecom.work. FAU - Huang, Peirong AU - Huang P AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: peirong.huang1@shgh.cn. FAU - Zhang, Jingting AU - Zhang J AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: jingting.zhang@shgh.cn. FAU - Luo, Dawei AU - Luo D AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: dawei.luo@shgh.cn. FAU - Zhang, Jingfa AU - Zhang J AD - Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases; Shanghai Clinical Research Center for Eye Diseases; Shanghai Key Clinical Specialty; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Eye Research Institute, Shanghai, China. Electronic address: jingfa.zhang@shgh.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20231222 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glycation End Products, Advanced) SB - IM MH - Humans MH - *Diabetic Retinopathy/metabolism MH - Endothelial Cells/metabolism MH - Poly(ADP-ribose) Polymerase Inhibitors MH - Retina/metabolism MH - Glucose/metabolism MH - *Hyperglycemia/metabolism MH - Glycation End Products, Advanced/metabolism MH - *Diabetes Mellitus/metabolism OTO - NOTNLM OT - Diabetic retinopathy OT - Glucose OT - Glucose metabolism OT - Glucose transport OT - Glucose transporter OT - SGLT2i COIS- Declaration of competing interest The authors have no conflicting financial interests. EDAT- 2023/12/25 00:42 MHDA- 2024/02/20 11:50 CRDT- 2023/12/24 19:25 PHST- 2023/08/02 00:00 [received] PHST- 2023/12/02 00:00 [revised] PHST- 2023/12/18 00:00 [accepted] PHST- 2024/02/20 11:50 [medline] PHST- 2023/12/25 00:42 [pubmed] PHST- 2023/12/24 19:25 [entrez] AID - S0925-4439(23)00361-7 [pii] AID - 10.1016/j.bbadis.2023.166995 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2024 Mar;1870(3):166995. doi: 10.1016/j.bbadis.2023.166995. Epub 2023 Dec 22.