Meyer Johanna, Cunea Alexander, Sonntag-Bensch Dagmar, Welker Pia, Licha Kai, Holz Frank G, Schmitz-Valckenberg Steffen
Department of Ophthalmology, University of Bonn, Bonn, Germany.
mivenion GmbH, Berlin, Germany.
Invest Ophthalmol Vis Sci. 2014 Sep 4;55(10):6204-12. doi: 10.1167/iovs.13-13617.
We investigated a novel formulation of indocyanine green (ICG/HS 15) in an animal model of laser-induced choroidal neovascularization (CNV).
The ICG was formulated with the nonionic solubilizer and emulsifying agent Kolliphor HS 15 to create ICG/HS 15 to improve the chemical stability and fluorescence efficacy. In vivo imaging was performed in rats that had undergone laser photocoagulation. Retinal uptake and fluorescence intensity of ICG and ICG/HS 15 were compared following intravenous injection of 3 dosages (0.05, 0.1, and 0.15 mg/kg body weight) at 7, 14, and 21 days following laser treatment. Postmortem analysis included histology with frozen sections and flat mounts.
Immediately following injection of ICG or ICG/HS 15, a strong fluorescence was visible in the retinal vasculature and at the site of laser lesions. Pixel intensity was higher for ICG/HS 15 compared to conventional ICG at 8 minutes after injection for all different injection days and dosages. Over time, a continuous decrease of the fluorescent signal was observed for up to 60 minutes to baseline level. Flow cytometry data showed an increased uptake of micellar dye of macrophages and endothelial cells. Histology revealed an accumulation of the micellar dye within the laser lesion.
Micelle formulated ICG can be visualized in the retinal vasculature and laser-induced CNV in vivo and ex vivo. Micellar ICG/HS 15 showed in vivo stronger signal intensity when compared to ICG for all tested dosages. Following further investigations, ICG/HS 15 may be evaluated in patients with retinal and choroidal diseases for more refined diagnosis.
我们在激光诱导脉络膜新生血管(CNV)的动物模型中研究了吲哚菁绿的一种新型制剂(ICG/HS 15)。
将吲哚菁绿与非离子增溶剂和乳化剂聚氧乙烯氢化蓖麻油HS 15配制成ICG/HS 15,以提高其化学稳定性和荧光效率。对接受激光光凝的大鼠进行体内成像。在激光治疗后7天、14天和21天,静脉注射3种剂量(0.05、0.1和0.15 mg/kg体重)的吲哚菁绿和ICG/HS 15后,比较它们在视网膜的摄取情况和荧光强度。死后分析包括冰冻切片和平铺标本的组织学检查。
注射吲哚菁绿或ICG/HS 15后,立即在视网膜血管和激光损伤部位可见强烈荧光。在所有不同的注射天数和剂量下,注射后8分钟时,ICG/HS 15的像素强度均高于传统吲哚菁绿。随着时间的推移,荧光信号持续下降长达60分钟至基线水平。流式细胞术数据显示巨噬细胞和内皮细胞对胶束染料的摄取增加。组织学检查显示胶束染料在激光损伤部位积聚。
胶束制剂的吲哚菁绿在体内和体外的视网膜血管及激光诱导的CNV中均可被可视化。与所有测试剂量的吲哚菁绿相比,胶束ICG/HS 15在体内显示出更强的信号强度。经过进一步研究后,ICG/HS 15可在视网膜和脉络膜疾病患者中进行评估,以实现更精确的诊断。