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 elucidat ed. The present study has investigated the capacity of TA to modulate the e xpression of adhesion molecules and permeability using a human epithelial c ell 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 restin g and phorbol myristate acetate (PMA)- or interferon-gamma (IFN-gamma)- and /or tumour necrosis factor-alpha (TNF-alpha)-activated cells using flow cyt ometry and immunocytochemistry. Additionally, ECV304 cells were grown to co nfluence in uncoated Transwell chambers; transepithelial resistance (TER) a cross resting and PMA-activated cells was monitored. TA significantly decre ased 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 b oth 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, su ggesting re-establishment of the BRB and down-regulation of inflammatory ma rkers are the principal effects of intravitreal TA in vivo. The results fur ther indicate that TA has the potential to influence cellular permeability, including the barrier function of the retinal pigment epithelium (RPE) in AMD-affected retinae.