Oxidized low density lipoprotein-induced senescence of retinal pigment epithelial cells is followed by outer blood-retinal barrier dysfunction

Jin Hyoung Kim, Sung-Joon Lee, Jeong Hun Kim, Kyu Won Kim, Young Suk Yu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Age-related macular degeneration is the most common cause of vision loss in the elderly, which starts from aging processes of retinal pigment epithelial cells. Among variable risk factors in occurrence and progression of age-related macular degeneration, oxidized low density lipoprotein could be causally involved in pathobiological changes of RPE cells. Herein we showed that oxidized low density lipoprotein-induced senescence of retinal pigment epithelial cells is followed by outer blood-retinal barrier dysfunction. Under sub-lethal concentration, oxidized low density lipoprotein could promote advanced senescence of retinal pigment epithelial cells. Interestingly expression of CRALBP and RPE 65, indicators of retinal pigment epithelial cell differentiation, was decreased by oxidized low density lipoprotein. In addition, oxidized low density lipoprotein induced reactive oxygen species production and up-regulated inflammatory factors such as tumor necrosis factor-α and vascular endothelial growth factor, when β-catenin, a critical mediator of the canonical Wnt pathway, was also elevated. Oxidized low density lipoprotein increased paracellular permeability of retinal pigment epithelial cells, when zonula occludens-1 at intercellular junctions markedly decreased as well. Furthermore, in retinal pigment epithelial cells and choriocapillaris of human apolipoprotein E2 transgenic mouse eye, increased vascular endothelial growth factor and decreased zonula occludens-1 expression was observed. Therefore, our results suggest that oxidized low density lipoprotein could promote senescence of retinal pigment epithelial cells which leads to induce outer blood-retinal barrier dysfunction as an early pathogenesis of age-related macular degeneration.

Original languageEnglish
Pages (from-to)808-814
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number5
DOIs
Publication statusPublished - 2012 May 1

Keywords

  • Outer blood-retinal barrier
  • Oxidized low density lipoprotein
  • Retinal pigment epithelial cell
  • Senescence

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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