2. Academic Validation
  3. Elimination of senescent cells inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells

Elimination of senescent cells inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells

  • Exp Eye Res. 2022 Oct;223:109207. doi: 10.1016/j.exer.2022.109207.
Furong Gao 1,  Lei Wang 2,  Binxin Wu 3,  Qingjian Ou 4,  Haibin Tian 3,  Jingying Xu 4,  Caixia Jin 3,  Jieping Zhang 5,  Juan Wang 4,  Lixia Lu 6,  Guo-Tong Xu 7
Affiliations

Affiliations

  • 1 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, 389 Xincun Road Shanghai, 200065, China; Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai, 200092, China. Electronic address: frgao@tongji.edu.cn.
  • 2 Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 3 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, 389 Xincun Road Shanghai, 200065, China; Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 4 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, 389 Xincun Road Shanghai, 200065, China.
  • 5 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, 389 Xincun Road Shanghai, 200065, China; Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 6 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, 389 Xincun Road Shanghai, 200065, China; Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai, 200092, China. Electronic address: lulixia@tongji.edu.cn.
  • 7 Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, 389 Xincun Road Shanghai, 200065, China; Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China. Electronic address: gtxu@tongji.edu.cn.
PMID: 35926646 DOI: 10.1016/j.exer.2022.109207
Abstract

Age-related macular degeneration (AMD) is one of the most common leading causes of irreversible blindness, and there is no effective treatment for it. It has been reported that aging is the greatest risk factor for AMD, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of AMD. To clarify the relationship between senescence and EMT in RPE cells, we used the replicative senescence model, H2O2- and/or Nutlin3a-induced senescence model, and low-density and/or TGF-β-induced EMT model to detect the expression of senescence-, RPE- and EMT-related genes, and assessed the motility of cells by using a scratch wound migration assay. The results showed that replicative senescence of RPE cells was accompanied by increased expression of EMT markers. However, senescent RPE cells themselves did not undergo EMT, as the H2O2and Nutlin3a treated cells showed no increase in EMT characteristics, including unchanged or decreased expression of EMT markers and decreased motility. Furthermore, conditioned medium (CM) from senescent cells induced EMT in presenescent RPE cells, and EMT accelerated the process of senescence. Importantly, dasatinib plus quercetin, which selectively eliminates senescent cells, inhibited low-density-induced EMT in RPE cells. These findings provide a better understanding of the interconnection between senescence and EMT in RPE cells. Removal of senescent cells by certain methods such as senolytics, might be a promising potential approach to prevent or delay the progression of RPE-EMT-related retinal diseases such as AMD.

Keywords

Age-related macular degeneration; Epithelial-mesenchymal transition; Retinal pigment epithelium; Senescence.

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