Quantitative proteomics reveals β2 integrin-mediated cytoskeletal rearrangement in vascular endothelial growth factor (VEGF)- induced retinal vascular hyperpermeability

Dong Hyun Jo, Jingi Bae, Sehyun Chae, Jin Hyoung Kim, Jong Hee Han, Daehee Hwang, Sang Won Lee, Jeong Hun Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Retinal vascular hyperpermeability causes macular edema, leading to visual deterioration in retinal diseases such as diabetic retinopathy and retinal vascular occlusion. Dysregulation of junction integrity between endothelial cells by vascular endothelial growth factor (VEGF) was shown to cause retinal vascular hyperpermeability. Accordingly, anti-VEGF agents have been used to treat retinal vascular hyperpermeability. However, they can confer potential toxicity through their deleterious effects on maintenance and survival of neuronal and endothelial cells in the retina. Thus, it is important to identify novel therapeutic targets for retinal vascular hyperpermeability other than VEGF. Here, we prepared murine retinas showing VEGF-induced vascular leakage from superficial retinal vascular plexus and prevention of VEGF-induced leakage by anti-VEGF antibody treatment. We then performed comprehensive proteome profiling of these samples and identified retinal proteins for which abundances were differentially expressed by VEGF, but such alterations were inhibited by anti-VEGF antibody. Functional enrichment and network analyses of these proteins revealed the β2 integrin pathway, which can prevent dysregulation of junction integrity between endothelial cells through cytoskeletal rearrangement, as a potential therapeutic target for retinal vascular hyperpermeability. Finally, we experimentally demonstrated that inhibition of the β2 integrin pathway salvaged VEGF-induced retinal vascular hyperpermeability, supporting its validity as an alternative therapeutic target to anti-VEGF agents.

Original languageEnglish
Pages (from-to)1681-1691
Number of pages11
JournalMolecular and Cellular Proteomics
Volume15
Issue number5
DOIs
Publication statusPublished - 2016 May

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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