Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration.
Whilst animal studies and a pilot clinical trial suggest that intravitreal triamcinolone acetonide (TA) may be useful in the treatment of age-related macular degeneration (AMD), its mode of action remains to be fully elucidated. The present study has investigated the capacity of TA to modulate the expression of adhesion molecules and permeability using a human epithelial cell line (ECV304) as a model of the outer blood-retinal barrier (BRB). The influence of TA on the expression of ICAM-1 and MHC-I was studied on resting and phorbol myristate acetate (PMA)- or interferon-gamma (IFN-gamma)- and/or tumour necrosis factor-alpha (TNF-alpha)-activated cells using flow cytometry and immunocytochemistry. Additionally, ECV304 cells were grown to confluence in uncoated Transwell chambers; transepithelial resistance (TER) across resting and PMA-activated cells was monitored. TA significantly decreased the paracellular permeability of ECV304 cells and down-regulated ICAM-1 expression, consistent with immunocytochemical observations. PMA-induced permeability changes were dose-dependent and TA decreased permeability of both resting and PMA-activated monolayers. MHC-I expression by ECV304 cells however, was not significantly affected by TA treatment. The modulation of TER and ICAM-1 expression in vitro correlate with clinical observations, suggesting re-establishment of the BRB and down-regulation of inflammatory markers are the principal effects of intravitreal TA in vivo. The results further indicate that TA has the potential to influence cellular permeability, including the barrier function of the retinal pigment epithelium (RPE) in AMD-affected retinae.
Penfold
P L
PL
Department of Clinical Ophthalmology, University of Sydney, Sydney, Australia. ppenfold@eye.usyd.edu.au
Wen
L
L
Madigan
M C
MC
Gillies
M C
MC
King
N J
NJ
Provis
J M
JM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008268:Macular Degeneration / Q000188:drug therapy / Q000276:immunology; D008854:Microscopy, Electron; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1; D014222:Triamcinolone Acetonide; D013755:Tetradecanoylphorbol Acetate