Rho GTPases control ciliary epithelium cells proliferation and progenitor profile induction in vivo

Carolina Beltrame Del Debbio1, Marinilce Fagundes Santos, Chao Yun Irene Yan

  • 1Department of Cell and Developmental Biology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.

Abstract

Insights

Modulating Rho GTPases in mouse ciliary epithelium affects retinal progenitor gene expression and cell proliferation. This suggests a new strategy for retinal repair by controlling these key cellular mechanisms.

Area of Science:

  • Cell Biology
  • Ophthalmology
  • Regenerative Medicine

Background:

  • Rho GTPases are crucial for cytoskeleton organization and signaling pathways regulating cell functions.
  • The ciliary epithelium (CE) in the mouse retina contains progenitor/stem cells.

Purpose of the Study:

  • To investigate the impact of Rho GTPases on cell cycle regulation and progenitor gene expression in mouse CE.
  • To explore the potential of CE progenitor/stem cells for retinal repair.

Main Methods:

  • Rho GTPases were activated or inhibited in mouse CE.
  • Protein localization, cell proliferation markers (p27kip, p16INK4a, Ki67), and progenitor markers (Pax6, Chx10) were analyzed.

Main Results:

  • Rho GTPase activation increased coexpression of progenitor markers Pax6 and Chx10 without affecting proliferation.
  • Rho GTPase inactivation boosted cell proliferation and enhanced growth factor effects.
  • Specific inhibition of Rac1 or ROCK increased proliferation markers and decreased cell cycle inhibitors.

Conclusions:

  • Rho GTPase modulation influences retinal progenitor gene expression and proliferation in adult mouse CE.
  • Targeting Rho GTPases offers a potential therapeutic approach for retinal repair through proliferation and reprogramming mechanisms.

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