Modulation of permeability and adhesion molecule expression by human choroidal endothelial cells.
OBJECTIVE
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 IFNgamma, TNFalpha, 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 IFNgamma, TNFalpha, and TA on paracellular permeability of CEC monolayers were assessed in transendothelial cell resistance (TER) assays.


RESULTS
Both IFNgamma and TNFalpha significantly upregulated expression of ICAM1 and MHC-I on CECs. Expression of VCAM1 was induced after stimulation with both IFNgamma and TNFalpha, whereas expression of MHC-II was induced only by stimulation with IFNgamma. Cytokine-induced expression of ICAM1, MHC-I, and MHC-II antigen by CECs was significantly downregulated by TA. IFNgamma 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.
Save Sight Institute and Department of Clinical Ophthalmology, University of Sydney, New South Wales, Australia. ppenfold@eye.usyd.edu.au
Philip L
PL
Penfold
Li
L
Wen
Michele C
MC
Madigan
Nicholas J C
NJ
King
Jan M
JM
Provis
D000328:Adult; D002829:Choroid / Q000098:blood supply*; D016207:Cytokines / Q000494:pharmacology*; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008875:Middle Aged; D010539:Permeability / Q000187:drug effects; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D016207:Cytokines; D005938:Glucocorticoids; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014222:Triamcinolone Acetonide