June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A Wnt mimic as a therapeutic approach to treat partial limbal stem cell deficiency: an in vitro model using single human limbal stem/progenitor cells
Author Affiliations & Notes
  • Clemence Bonnet
    Cornea, Jules Stein Eye Institute, Los Angeles, California, United States
    Cornea, Cochin hospital Ophthalmology Department, PARIS, France
  • Sheyla Gonzalez
    Cornea, Jules Stein Eye Institute, Los Angeles, California, United States
  • Sophie X. Deng
    Cornea, Jules Stein Eye Institute, Los Angeles, California, United States
  • Jie J Zheng
    Cornea, Jules Stein Eye Institute, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Clemence Bonnet None; Sheyla Gonzalez None; Sophie Deng Novartis US, Code C (Consultant/Contractor), Dompe US, Code C (Consultant/Contractor), Claris Biotherapeutics, Code C (Consultant/Contractor); Jie Zheng None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3138. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Clemence Bonnet, Sheyla Gonzalez, Sophie X. Deng, Jie J Zheng; A Wnt mimic as a therapeutic approach to treat partial limbal stem cell deficiency: an in vitro model using single human limbal stem/progenitor cells. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3138.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To assess the effects of Wnt acitvation in a in vitro model of partial limbal stem cell deficiency.

Methods : To mimic LSCD from a chemical burn, one of the most frequent etiologies of LSCD worldwide, an in vitro alkali burn model was developed using single limbal epithelial cells. The model was established by exposing cultured LSCs to various concentrations of sodium hydroxide. After model validation, Wnt activation was attained in the damaged LSCs by treating the cells with lithium chloride (LiCl), a widely used GSK-3β inhibitor, and a small-molecule Wnt mimic, respectively. The cell phenotype (% of cytokeratin 12, 14, p63 bright cells, vimentin) and proliferation were assessed.

Results : A progressive loss of their stem/progenitor phenotype was observed: the percentage of p63bright cells (putative LSCs marker) and cytokeratin (K)14+ cells (undifferentiation marker) decreased while the percentage of K12+ (differentiation marker) increased. After 18 hours of treatment by Wnt activators, LSCs proliferation was increased. The LSC phenotype was recovered in the Wnt mimic and the LiCl groups, while the untreated cells lost their phenotype and did not proliferate. In the Wnt mimic group, the percentage of p63bright cells was significantly higher in LiCl-treated cells (2.27 fold change increase, p<0.05) and Wnt mimic-treated cells (4.12 fold change increase, p<0.05) while the percentage of K12+ cells was significantly lower.

Conclusions : These findings suggest that the local Wnt activation may rescue LSCs upon alkaline injury.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×