Triamcinolone acetonide suppresses early proangiogenic response in retinal pigment epithelial cells after photodynamic therapy in vitro.
OBJECTIVE
To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic therapy (PDT), especially focusing on their change in the presence of triamcinolone acetonide.


METHODS
Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were exposed to 5 microg/ml verteporfin combined with or without 1 microg/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or without 1 microg/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed.


RESULTS
Cellular uptake of verteporfin was not significantly changed by the presence of 1 microg/ml triamcinolone acetonide. In addition, 0.01-0.1 microg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 microg/ml did not affect the cell viability but significantly increased VEGF (p<0.001) and reduced PEDF (p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF (p<0.001) and decrease in PEDF (p = 0.001).


CONCLUSIONS
VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.
Obata
R
R
Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. yanagi-tky@umin.ac.jp
Iriyama
A
A
Inoue
Y
Y
Takahashi
H
H
Tamaki
Y
Y
Yanagi
Y
Y
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005136:Eye Proteins / Q000032:analysis; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009414:Nerve Growth Factors / Q000032:analysis; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000098:blood supply* / Q000187:drug effects; D011166:Porphyrins / Q000493:pharmacokinetics / Q000494:pharmacology; D011480:Protease Inhibitors / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015843:Serpins / Q000032:analysis; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000077362:Verteporfin; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D005938:Glucocorticoids; D009414:Nerve Growth Factors; D017319:Photosensitizing Agents; D011166:Porphyrins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D015843:Serpins; D014222:Triamcinolone Acetonide; D042461:Vascular Endothelial Growth Factor A; D000077362:Verteporfin; D000099174:Pigment Epithelium-Derived Factor