title: Blockade of vascular endothelial growth factor receptor 1 prevents inflammation and vascular leakage in diabetic retinopathy.
abstract: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. The objective of this study is to investigate the effects of vascular endothelial growth factor receptor 1 (VEGFR1) blockade on the complications of DR. Experimental models of diabetes were induced with streptozotocin (STZ) treatment or Insulin2 gene mutation (Akita) in mice. Protein expression and localization were examined by western blots (WB) and immunofluorescence (IF). mRNA expression was quantified by PCR array and real-time PCR. The activity of VEGFR1 signaling was blocked by a neutralizing antibody called MF1. Vascular leakage was evaluated by measuring the leakage of [(3)H]-mannitol tracer into the retina and the IF staining of albumin. VEGFR1 blockade significantly inhibited diabetes-related vascular leakage, leukocytes-endothelial cell (EC) adhesion (or retinal leukostasis), expression of intercellular adhesion molecule- (ICAM-) 1 protein, abnormal localization and degeneration of the tight junction protein zonula occludens- (ZO-) 1, and the cell adhesion protein vascular endothelial (VE) cadherin. In addition, VEGFR1 blockade interfered with the gene expression of 10 new cytokines and chemokines: cxcl10, il10, ccl8, il1f6, cxcl15, ccl4, il13, ccl6, casp1, and ccr5. These results suggest that VEGFR1 mediates complications of DR and targeting this signaling pathway represents a potential therapeutic strategy for the prevention and treatment of DR.
authors.affiliation: Guangxi Tumor Hospital & Institute, Nanning, Guangxi 530021, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Ophthalmology, the Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Changsha Aier Eye Hospital, Changsha, Hunan 410015, China ; Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, China ; Wilmer Eye Institute, Johns Hopkins University School of Medicine, M017 Robert H. and Clarice Smith Building, 400 N Broadway, Baltimore, MD 21287, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Changsha Aier Eye Hospital, Changsha, Hunan 410015, China ; Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, China ; Wilmer Eye Institute, Johns Hopkins University School of Medicine, M017 Robert H. and Clarice Smith Building, 400 N Broadway, Baltimore, MD 21287, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, M017 Robert H. and Clarice Smith Building, 400 N Broadway, Baltimore, MD 21287, USA.
authors.forename: Dorothy
authors.identifier: 0000-0003-3769-2832
authors.initials: D
authors.lastname: Kim
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, M017 Robert H. and Clarice Smith Building, 400 N Broadway, Baltimore, MD 21287, USA.
authors.forename: Hu
authors.identifier: 0000-0003-2843-0320
authors.initials: H
authors.lastname: Huang
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