Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells
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Zhao-Hui Li. Department of Ophthalmology, the Chinese PLA General Hospital, Beijing 100853, China. zhaohuili650@hotmail.com

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    Abstract:

    AIM: To identify the effect and regulatory mechanism of amyloid β (Aβ) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify Aβ role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The model of Aβ25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aβ protein on RPE cells in vitro. Based on Aβ protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of Aβ protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay. RESULTS: The number of RPE cells, treated with Aβ25-35 from 0.3 to 60 μmol/L, significantly reduce (P<0.01), and had the dose-dependent effect. Aβ protein 60 μmol/L inhibits the G1/S phase transition (P<0.01) and down-regulated cyclin E mRNA level (P<0.01). Similarly, Aβ25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-κB) activity and phosphorylated Iκ-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the Aβ, the cell numbers, NF-κB activity, phosphorylated Iκ-Ba level, receptor for advanced glycation endproducts (RAGE) gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-κB signaling pathway involved in the regulation of Aβ protein on RPE cell apoptosis and proliferation. CONCLUSION: Aβ protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-κB signaling pathway in RPE cell.

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Zi Ye, Shou-Zhi He, Zhao-Hui Li. Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells. Int J Ophthalmol, 2018,11(6):929-934

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Publication History
  • Received:April 19,2017
  • Revised:September 15,2017
  • Adopted:
  • Online: June 12,2018
  • Published: