Spandau U H M, Sauder G, Schubert U, Hammes H-P, Jonas J B
Augenklinik, Klinikum Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany.
Br J Ophthalmol. 2005 Jun;89(6):745-7. doi: 10.1136/bjo.2004.052563.
To assess the effect of crystalline triamcinolone acetonide on retinal endothelial cell proliferation in vivo and in vitro.
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.
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).
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.
评估曲安奈德晶体对体内和体外视网膜内皮细胞增殖的影响。
体外分析采用发芽试验。用碱性成纤维细胞生长因子(bFGF)刺激牛视网膜内皮细胞,并与不同浓度的曲安奈德(0.05mg/ml至8mg/ml)孵育。体内分析采用早产儿视网膜病变(ROP)模型。16只C57BL/J6小鼠从出生后第7天至第12天暴露于75%氧气中。在第12天,将曲安奈德玻璃体内注射到一只眼睛(“研究眼”),对侧眼睛注射等渗盐水(“对照眼”)。在第17天,处死小鼠并摘除眼睛,用于视网膜前新生血管形成的定量分析。4只未暴露的小鼠作为阴性对照。
发芽试验表明,从0.05mg曲安奈德/ml(无抑制)到3mg曲安奈德/ml(完全抑制),对牛视网膜内皮细胞增殖的抑制呈剂量依赖性。剂量超过2mg/ml会导致内皮细胞发生细胞毒性变化。ROP模型显示,研究组的新生血管细胞计数比对照组显著降低58%(每个组织学切片6.35(标准差2.1)个细胞对14.9(标准差5.3)个细胞;p<0.005)。
曲安奈德在体内和体外均抑制bFGF诱导的视网膜内皮细胞增殖。这些发现有助于理解曲安奈德对视网膜新生血管形成的作用方式和效果。