title: Advanced glycation end products delay corneal epithelial wound healing through reactive oxygen species generation.
abstract: Delayed healing of corneal epithelial wounds is a serious complication in diabetes. Advanced glycation end products (AGEs) are intimately associated with the diabetic complications and are deleterious to the wound healing process. However, the effect of AGEs on corneal epithelial wound healing has not yet been evaluated. In the present study, we investigated the effect of AGE-modified bovine serum albumin (BSA) on corneal epithelial wound healing and its underlying mechanisms. Our data showed that AGE-BSA significantly increased the generation of intracellular ROS in telomerase-immortalized human corneal epithelial cells. However, the generation of intracellular ROS was completely inhibited by antioxidant N-acetylcysteine (NAC), anti-receptor of AGEs (RAGE) antibodies, or the inhibitor of NADPH oxidase. Moreover, AGE-BSA increased NADPH oxidase activity and protein expression of NADPH oxidase subunits, p22phox and Nox4, but anti-RAGE antibodies eliminated these effects. Furthermore, prevention of intracellular ROS generation using NAC or anti-RAGE antibodies rescued AGE-BSA-delayed epithelial wound healing in porcine corneal organ culture. In conclusion, our results demonstrated that AGE-BSA impaired corneal epithelial wound healing ex vivo. AGE-BSA increased intracellular ROS generation through NADPH oxidase activation, which accounted for the delayed corneal epithelial wound healing. These results may provide better insights for understanding the mechanism of delayed healing of corneal epithelial wounds in diabetes.
authors: Department of Ophthalmology, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, People's Republic of China.
authors: Long
authors: L
authors: Shi
authors: Hongmei
authors: H
authors: Chen
authors: Xiaoming
authors: X
authors: Yu
authors: Xinyi
authors: X
authors: Wu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D034421:Sus scrofa; D019098:Telomerase / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D019255:NADPH Oxidases; D019098:Telomerase; D000111:Acetylcysteine
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