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Modulation of Permeability and Adhesion Molecule Expression by Human Choroidal Endothelial Cells

¹ From the Save Sight Institute and the ² Departments of Clinical Ophthalmology, ³ Anatomy and Histology, and ⁴ Pathology, University of Sydney, New South Wales, Australia.

PURPOSE. The therapeutic potential of TA, an anti-inflammatory glucocorticoid, for the treatment of exudative retinopathy has been examined in several independent clinical studies. The modulation of permeability and adhesion molecule expression of an epithelial cell line has been described in vitro, with the use of cytokines and triamcinolone acetonide (TA). In the current study, the influence of proinflammatory cytokines and TA on permeability and adhesion molecule expression in human choroidal endothelial cells (CECs) was investigated.

METHODS. Human CEC isolates treated with IFN, TNF, and TA were evaluated by flow cytometry and immunocytochemistry for expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and major histocompatibility complex (MHC)-I and -II. The effects of IFN, TNF, and TA on paracellular permeability of CEC monolayers were assessed in transendothelial cell resistance (TER) assays.

RESULTS. Both IFN and TNF significantly upregulated expression of ICAM1 and MHC-I on CECs. Expression of VCAM1 was induced after stimulation with both IFN and TNF, whereas expression of MHC-II was induced only by stimulation with IFN. Cytokine-induced expression of ICAM1, MHC-I, and MHC-II antigen by CECs was significantly downregulated by TA. IFN stimulation also increased permeability of CEC monolayers, whereas subsequent TA treatment decreased permeability of CEC monolayers.

CONCLUSIONS. Human CEC isolates provide a useful in vitro model to study choroidal neovascular membrane characteristics and their potential response to pro- and anti-inflammatory agents. In addition, the results indicate that TA has the capacity to reduce adhesion molecule expression and permeability of choroidal vessels in vitro, confirming its potential as a therapeutic agent for treatment of exudative macular degeneration.

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