title: The Neuropilin-1 Inhibitor, ATWLPPR Peptide, Prevents Experimental Diabetes-Induced Retinal Injury by Preserving Vascular Integrity and Decreasing Oxidative Stress.
abstract: Neuropilin-1 (NRP-1) is a transmembrane glycoprotein. As a VEGF co-receptor, NRP1 significantly enhances VEGFR2 signaling and promotes vascular permeability and migration. The purpose of this study was to evaluate the effects of an NRP-1 inhibitor, ATWLPPR peptide, on the early stages of diabetic retinopathy. Eight-week-old male C57BL/6 mice were divided into three groups: a Normal group, a Diabetes (DB) ATWLPPR treatment group and a DB saline group. Electroretinography (ERG), fundus fluorescence angiography (FFA) and leukostasis were examined to evaluate the retinal injury induced by diabetes at the end of the fifth week after STZ injection. Occludin expression and extravasation of albumin were measured to determine the extent of vascular injury. The oxidative stress level and the levels of inflammation-associated proteins were also assayed. The results indicated that treatment with ATWLPPR prevents the abnormal condition of ERG (amplitudes of b-wave decreased and implicit time increased) and vascular injury (occludin degradation and increase in extravasated albumin). These effects were associated with a reduction in the oxidase stress level and the expression of VEGF, GFAP, and ICAM-1. We conclude that ATWLPPR, an NRP-1 inhibitor, may reduce the early retinal damage induced by diabetes by preserving vascular integrity and decreasing the oxidative stress level. Blockade of NRP-1 may be a new therapeutic strategy for the early stages of DR.
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Shuaiwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Mengling
authors.initials: M
authors.lastname: Li
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital of Henan University, Kaifeng 475001, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Henan University, Kaifeng 475001, China.
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Yang
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Ji
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Ji
authors.affiliation: Medical College of Henan University, Kaifeng, 475004, China.
authors.forename: Yanzhang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C000599882:Ala-Thr-Trp-Leu-Pro-Pro-Arg; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor