Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration

Abstract

SUMMARYWhilst 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-g)-and/or tumour necrosis factor-alpha (TNF-a )-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.

Intravitreal triamcinolone for macular detachment following panretinal photocoagulation

“…Corticosteroids may also downregulate the production of vascular endothelial growth factor, a known vascular permeability factor. 5 Triamcinolone acetonide, a corticosteroid suspension, has been shown experimentally to reduce breakdown of the blood-retinal barrier. 6 After intravitreal injection, the drug is delivered rapidly to its site of action with maximal bioavailability.…”

“…5 The patient was evaluated for the possibility of underlying causes such as diabetes, ocular ischaemia, vascular occlusion, and intraocular inflammation. We can only speculate on the pathogenesis of the development of NVD as our attempts to identify an underlying cause were unsuccessful.…”

Subretinal fluid from rhegmatogenous retinal detachment and blood induces the expression of ICAM-1 in the human retinal pigment epithelium (ARPE-19) in vitro

“…45 Both drugs have anti-inflammatory effects and they had been reported to inhibit cytokine-induced ICAM-1 expression in vitro. [20][21][22]46,47 Therefore, our study also evaluated the effects of the two drugs on ICAM-1 expression induced by SRF. The results were negative; neither drug significantly reduced ICAM-1 expression in RPE cells stimulated by SRF.…”

“…In past studies, TNF-a or IFN-g were used to stimulate the expression of ICAM-1 and GS or TA countered the actions. [20][21][22] However, they may not be major components of SRF, and this could be the reason for the different results. In our SRF array (data not shown) and a past report, 30 IL-6 was the major component of SRF, and the ICAM-1 expression pathway induced by IL-6 in RPE cells may be different from those induced by TNF-a or IFN-g. GS had been shown to downregulate ICAM-1 expression through the prevention of NF-kB activity and GS-activated STAT1 nuclear translocation in RPE cells, 20 but SRF may not induce ICAM-1 expression by the same pathway.…”

“…21 In a previous study, it was demonstrated that TA downregulated cytokine-induced expression of ICAM-1 in human choroidal endothelial cells. 22 We conducted this study to evaluate whether SRF from RRD and blood induce the expression of ICAM-1 in RPE cells. We also evaluated if two anti-inflammatory drugs, GS and TA, inhibit SRF-induced ICAM-1 expression in RPE cells.…”