June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Connexin 50 Inhibits Lens Epithelial Cells Migration and Epithelial-Mesenchymal Transition
Author Affiliations & Notes
  • Bo Ma
    The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
    Ophthalmology in the First Affiliated Hospital of Xi’an Jiaotong University, Xi'an Jiaotong University, Xi'an, Shaanxi, China
  • Zhen Li
    The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Guangyan Wang
    The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Sumin Gu
    The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Jean X. Jiang
    The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Footnotes
    Commercial Relationships   Bo Ma None; Zhen Li None; Guangyan Wang None; Sumin Gu None; Jean Jiang None
  • Footnotes
    Support  NIH EY012085
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5119. doi:
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    • Get Citation

      Bo Ma, Zhen Li, Guangyan Wang, Sumin Gu, Jean X. Jiang; Connexin 50 Inhibits Lens Epithelial Cells Migration and Epithelial-Mesenchymal Transition. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5119.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Our previous results showed that connexin (Cx) 50 plays an important role in cell-cell adhesion, which has been known to inhibit cell migration and epithelial-mesenchymal transition (EMT). The purpose of the current study is to test the hypothesis that cell adhesive function of Cx50 prevents lens epithelial cell migration and EMT, and the occurrence of posterior capsule opacification (PCO) development.

Methods : The primary embryonic chick lens cells (CLCs) and the embryonic chick lens ex vivo mimicking wound repair model were infected with RCAS(A) retrovirus containing vehicle, Cx50WT, and Cx50 dominant negative mutants P88S (hemichannel and gap junction), E488K (gap junction), H156N (hemichannel); and Cx50 adhesion-impaired E2 domain mutants: G186S and W188P. These cultured cells were treated with 10 ng/mL TGF-β2 and western blotting and immunofluorescence were used to assess the expression of protein markers associated with cell adhesion, proliferation, migration and EMT. A study of extracapsular lens extraction (ECLE), was performed in WT and Cx50KO mice. The isolated eyeballs were processed for immunofluorescence to determine the expression of EMT, adhesion and ECM markers.

Results : TGF-β2 treatment decreased Cx50 expression while increased the α-SMA, fibronectin and N-cadherin expression in the CLCs, which was suppressed by overexpression of Cx50WT. Moreover, the lens epithelial cells (LECs), infected with Cx50WT, migration and EMT were significantly reduced compared to vehicle in ex vivo. However, Cx50 E2 domain mutants, G186S and W188P, significantly increased α-SMA, fibronectin and N-cadherin expressed in CLCs, and promoted cell migration in ex vivo. Interestingly, hemichannel-impaired mutant H156N, but not P88S and E488K with impaired gap junctions, has similar inhibitory function as Cx50WT. In addition, Cx50 was found to be co-localized with β-catenin on LECs surface and prevented TGF-β2-induced β-catenin nuclear translocation. Furthermore, the EMT markers expression in Cx50KO mice are significantly increased than that in WT mice.

Conclusions : The results suggest that Cx50 could effectively suppress LECs migration, EMT and prevent PCO development possibly via its interaction with β-catenin. The adhesive function of Cx50E2 domain is critical in inhibiting the EMT process. Moreover, Cx50 gap junctions but not hemichannels are likely to be involved in EMT development of LECs.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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