A2E, a component of lipofuscin, is pro-angiogenic in vivo

Aya Iriyama, Yuji Inoue, Hidenori Takahashi, Yasuhiro Tamaki, Woo Dong Jang, Yasuo Yanagi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A recent study in vitro demonstrated that a major lipofuscin component, A2E, serves as a retinoic acid receptor ligand. The current study investigated the effects of A2E on retinal pigment epithelial (RPE) cells in vivo and was performed to extend the understanding of the effects of A2E. Firstly, subretinal injection of A2E was performed and 3 weeks after the injection, and it was demonstrated that subretinal injection of A2E induced RPE cell death, and concomitant upregulation of vascular endothelial growth factor (VEGF) in the RPE and choroid. The upregulation of VEGF was attenuated by an RARa antagonist. Next we performed laser photocoagulation in mice that accumulated A2E either after subretinal injection, by Ccl2 gene knockout or by aging demonstrated that mice that accumulated A2E in the RPE, which showed higher rates of choroidal neobascularization (CNV) formation after weak laser injury than the controls and the formation of CNV was inhibited by an RARa antagonist in all models tested. The data suggest that A2E accumulation induces RPE cell death, and concomitant increase of VEGF. Accumulation of A2E alone is not sufficient to induce CNV in vivo, but induces the expression of VEGF in RPE and choroid. The mice that accumulated A2E in RPE cells are vulnerable to CNV development via RAR activation, at least in part.

Original languageEnglish
Pages (from-to)469-475
Number of pages7
JournalJournal of Cellular Physiology
Volume220
Issue number2
DOIs
Publication statusPublished - 2009 Aug 1

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Lipofuscin
Retinal Pigments
Vascular Endothelial Growth Factor A
Epithelial Cells
Injections
Choroid
Cell death
Lasers
Cell Death
Up-Regulation
Gene Knockout Techniques
Retinoic Acid Receptors
Light Coagulation
Genes
Aging of materials
Chemical activation
Ligands
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Iriyama, A., Inoue, Y., Takahashi, H., Tamaki, Y., Jang, W. D., & Yanagi, Y. (2009). A2E, a component of lipofuscin, is pro-angiogenic in vivo. Journal of Cellular Physiology, 220(2), 469-475. https://doi.org/10.1002/jcp.21792
Iriyama, Aya ; Inoue, Yuji ; Takahashi, Hidenori ; Tamaki, Yasuhiro ; Jang, Woo Dong ; Yanagi, Yasuo. / A2E, a component of lipofuscin, is pro-angiogenic in vivo. In: Journal of Cellular Physiology. 2009 ; Vol. 220, No. 2. pp. 469-475.
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Iriyama, A, Inoue, Y, Takahashi, H, Tamaki, Y, Jang, WD & Yanagi, Y 2009, 'A2E, a component of lipofuscin, is pro-angiogenic in vivo', Journal of Cellular Physiology, vol. 220, no. 2, pp. 469-475. https://doi.org/10.1002/jcp.21792

A2E, a component of lipofuscin, is pro-angiogenic in vivo. / Iriyama, Aya; Inoue, Yuji; Takahashi, Hidenori; Tamaki, Yasuhiro; Jang, Woo Dong; Yanagi, Yasuo.

In: Journal of Cellular Physiology, Vol. 220, No. 2, 01.08.2009, p. 469-475.

Research output: Contribution to journalArticle

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AU - Inoue, Yuji

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