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 language | English |
|---|---|
| Pages (from-to) | 808-814 |
| Number of pages | 7 |
| Journal | International Journal of Biochemistry and Cell Biology |
| Volume | 44 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2012 May 1 |
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Keywords
- Outer blood-retinal barrier
- Oxidized low density lipoprotein
- Retinal pigment epithelial cell
- Senescence
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
Cite this
Oxidized low density lipoprotein-induced senescence of retinal pigment epithelial cells is followed by outer blood-retinal barrier dysfunction. / Kim, Jin Hyoung; Lee, Sung-Joon; Kim, Jeong Hun; Kim, Kyu Won; Yu, Young Suk.
In: International Journal of Biochemistry and Cell Biology, Vol. 44, No. 5, 01.05.2012, p. 808-814.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxidized low density lipoprotein-induced senescence of retinal pigment epithelial cells is followed by outer blood-retinal barrier dysfunction
AU - Kim, Jin Hyoung
AU - Lee, Sung-Joon
AU - Kim, Jeong Hun
AU - Kim, Kyu Won
AU - Yu, Young Suk
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
KW - Outer blood-retinal barrier
KW - Oxidized low density lipoprotein
KW - Retinal pigment epithelial cell
KW - Senescence
UR - http://www.scopus.com/inward/record.url?scp=84862813425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862813425&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2012.02.005
DO - 10.1016/j.biocel.2012.02.005
M3 - Article
C2 - 22349216
AN - SCOPUS:84862813425
VL - 44
SP - 808
EP - 814
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
SN - 1357-2725
IS - 5
ER -