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Updated: Jan 24, 2026

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Inhibition of mTOR by Rapamycin Aggravates Corneal Epithelial Stem Cell Deficiency by Upregulating Inflammatory

Jong Woo Park1, Jung Hwa Ko1, Bo Hee Kim2

  • 1Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.

Stem Cells (Dayton, Ohio)
|May 19, 2019
PubMed

Insights

mTOR inhibition with rapamycin worsens corneal stem cell deficiency by increasing inflammation. Restoring IL-10 levels counteracts these detrimental effects, highlighting mTOR

Area of Science:

  • Ophthalmology
  • Stem Cell Biology
  • Immunology

Background:

  • Mammalian target of rapamycin (mTOR) signaling regulates stem cell function.
  • The role of mTOR in corneal epithelial stem cells (CESCs) during inflammation is unknown.

Purpose of the Study:

  • To investigate the effects of mTOR signaling on CESCs under sterile inflammation.
  • To elucidate the mechanisms by which mTOR inhibition impacts CESC survival and corneal inflammation.

Main Methods:

  • Utilized a mouse model of sterile inflammation-induced CESC deficiency.
  • Administered rapamycin (mTOR inhibitor) and assessed CESC apoptosis and inflammation.
  • Investigated the role of the interleukin-10 (IL-10)/signal transducer and activator of transcription 3 (STAT3) pathway.

Main Results:

  • mTOR inhibition with rapamycin promoted CESC apoptosis and aggravated disease.
  • Rapamycin's effect was mediated by increased neutrophilic inflammation, not direct toxicity.
  • Rapamycin downregulated the IL-10/STAT3 anti-inflammatory pathway.
  • IL-10 replenishment reversed the effects of rapamycin on inflammation and CESC apoptosis.

Conclusions:

  • mTOR signaling balances pro- and anti-inflammatory responses in the cornea.
  • mTOR inhibition exacerbates inflammation-induced damage to CESCs.
  • Targeting mTOR requires careful consideration of its impact on ocular inflammation and stem cell health.
Keywords:
ApoptosisCorneal epithelial stem cellInflammationInterleukin-10Mammalian target of rapamycinRapamycin

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