Effect of triamcinolone acetonide on proliferation of retinal endothelial cells in vitro and in vivo.
OBJECTIVE
To assess the effect of crystalline triamcinolone acetonide on retinal endothelial cell proliferation in vivo and in vitro.


METHODS
For in vitro analysis, a sprouting assay was employed. Bovine retinal endothelial cells were stimulated with basic fibroblast growth factor (bFGF) and incubated with different concentrations of triamcinolone acetonide (0.05 mg/ml to 8 mg/ml). For in vivo analysis, a retinopathy of prematurity (ROP) model was used. 16 C57BL/J6 mice were exposed to 75% oxygen from postnatal day 7 to day 12. On day 12, triamcinolone acetonide was intravitreally injected into one eye ("study eye") and isotonic saline into the contralateral eye ("control eye"). On day 17, the mice were sacrificed and the eyes removed for quantitative analysis of preretinal neovascularisation. Four non-exposed mice served as negative control.


RESULTS
The sprouting assay demonstrated a dose dependent inhibition of bovine retinal endothelial cell proliferation from 0.05 mg triamcinolone acetonide/ml (no inhibition) to 3 mg triamcinolone acetonide/ml (complete inhibition). Dosages of more than 2 mg/ml resulted in cytotoxic changes of endothelial cells. The ROP model demonstrated a significantly lower neovascular cell count of 58% in the study group compared to the control group (6.35 (SD 2.1) cells per histological section versus 14.9 (SD 5.3) cells; p<0.005).


CONCLUSIONS
Triamcinolone acetonide inhibits bFGF induced proliferation of retinal endothelial cells in vivo and in vitro. These findings contribute to understanding the mode of action and effects of triamcinolone acetonide on retinal neovascularisation.
Spandau
U H M
UH
Augenklinik, Klinikum Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. Ulrich_Spandau@yahoo.de
Sauder
G
G
Schubert
U
U
Hammes
H-P
HP
Jonas
J B
JB
D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects*; D012178:Retinopathy of Prematurity / Q000150:complications / Q000473:pathology; D014222:Triamcinolone Acetonide / Q000494:pharmacology* / Q000627:therapeutic use
D005938:Glucocorticoids; D016222:Fibroblast Growth Factor 2; D014222:Triamcinolone Acetonide