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Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

  • Authors:
    • Chaoqi Liu
    • Lining Cao
    • Shuai Yang
    • Linxinyu Xu
    • Pei Liu
    • Fang Wang
    • Ding Xu

  • View Affiliations

  • Published online on: November 10, 2014     https://doi.org/10.3892/ijmm.2014.1993
  • Pages: 169-176
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Abstract

Drusen are considered a hallmark characteristic of age‑related macular degeneration (AMD). In our previous study, we found that amyloid-β (Aβ) peptide, a component of drusen, induced the cells of the retinal pigment epithelium (RPE; RPE cells) to enter senescence; however, its effects in vivo remain unknown. Thus, the present study was carried out to explore the in vivo effects of Aβ peptide on RPE cell senescence and senescence-associated inflammation in C57BL/6 mice. C57BL/6 mice received a subretinal injection of Aβ(1-42) peptide; on day 7 post-injection, the mice were anesthetized and subjected to whole‑body perfusion with 4% paraformaldehyde (PFA) in PBS and the whole eyes were then enucleated. Retinal function was assessed by electroretinography (ERG), and the morphological characteristics of the retina were examined by light and electron microscopy. Fundus autofluorescence (FAF) was examined by confocal scanning laser ophthalmoscopy (cSLO). The expression of p16INK4a, a marker of cellular senescence, was examined by immunofluorescence staining and western blot analysis. The RPE-choroid was analyzed for cytokine expression by RT-PCR. In Aβ(1‑42)-injected mice, scotopic ERG responses declined. Degenerative alterations, including the disruption of the inner segment (IS)/outer segment (OS) junction and extensive vacuolation and thickness of Bruch's membrane (BrM) were observed under a a light microscope. The accumulation of vacuoles and the loss of basal infoldings in the RPE were identified using an electron microscope. FAF and p16INK4a expression increased in Aβ(1-42)-injected mice. In addition, Aβ(1-42) upregulated interleukin (IL)-6 and IL-8 gene expression in the RPE-choroid. In conclusion, our results confirm the effects of Aβ(1-42) peptide on RPE senescence in vivo. The Aβ-injected mice developed AMD-like ocular pathology. It is thus suggested that RPE cell senescence is a potential mechanistic link between inflammation and retinal degeneration.
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January-2015
Volume 35 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • Impact Factor: 5.7
  • Ranked Medicine Research and Experimental
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  • CiteScore: 12.3
  • CiteScore Rank: Q1: #28/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 1.022
  • SCImago Journal Rank (SJR): 1.167
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Spandidos Publications style
Liu C, Cao L, Yang S, Xu L, Liu P, Wang F and Xu D: Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration. Int J Mol Med 35: 169-176, 2015.
APA
Liu, C., Cao, L., Yang, S., Xu, L., Liu, P., Wang, F., & Xu, D. (2015). Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration. International Journal of Molecular Medicine, 35, 169-176. https://doi.org/10.3892/ijmm.2014.1993
MLA
Liu, C., Cao, L., Yang, S., Xu, L., Liu, P., Wang, F., Xu, D."Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration". International Journal of Molecular Medicine 35.1 (2015): 169-176.
Chicago
Liu, C., Cao, L., Yang, S., Xu, L., Liu, P., Wang, F., Xu, D."Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration". International Journal of Molecular Medicine 35, no. 1 (2015): 169-176. https://doi.org/10.3892/ijmm.2014.1993