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Human RPE cell apoptosis induced by activated monocytes is mediated by caspase-3 activation

Susan G Elner1, Ayako Yoshida, Zong-Mei Bian

  • 1Department of Ophthalmology, University of Michigan, Ann Arbor, USA.

Transactions of the American Ophthalmological Society
|February 20, 2004
PubMed
Abstract

Insights

Activated monocytes induce reactive oxygen metabolites (ROM) and apoptosis in human retinal pigment epithelial (HRPE) cells through cell-to-cell contact, partly via CD18 and ICAM-1. These findings suggest mechanisms that may impair HRPE cell function in retinal diseases.

Area of Science:

  • Ophthalmology
  • Immunology
  • Cell Biology

Background:

  • Human retinal pigment epithelial (HRPE) cells are crucial for retinal health.
  • Monocyte infiltration into the retina is observed in various retinal diseases.

Purpose of the Study:

  • To investigate the impact of activated monocytes on HRPE cell reactive oxygen metabolite (ROM) production and apoptosis.
  • To elucidate the mechanisms underlying monocyte-induced HRPE cell damage.

Main Methods:

  • HRPE cells were co-cultured with interferon-gamma (IFN-gamma)-stimulated human monocytes.
  • Apoptosis was assessed using TUNEL staining, PCNA, caspase-3 activation, and Western blot.
  • ROM production was monitored using dihydrotetramethylrosamine (H2TMRos).

Main Results:

  • Direct contact with activated monocytes significantly increased HRPE cell apoptosis (TUNEL-positive) and decreased proliferation (PCNA-positive).
  • Activated monocytes induced caspase-3 activation in HRPE cells, which was inhibited by Z-DEVD-fmk.
  • Inhibition of CD18 and ICAM-1 significantly reduced monocyte-induced HRPE cell apoptosis and ROM production.

Conclusions:

  • IFN-gamma-activated monocytes induce ROM and apoptosis in HRPE cells via cell-to-cell contact, involving CD18 and ICAM-1.
  • Caspase-3 activation is a key mediator of monocyte-induced HRPE cell apoptosis.
  • These findings highlight potential mechanisms contributing to HRPE cell dysfunction in retinal diseases with monocyte infiltration.

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