补体耗竭用人源化眼镜蛇毒因子治疗年龄相关性黄斑变性的小鼠模型。
Complement depletion with humanized cobra venom factor in a mouse model of age-related macular degeneration.
机构信息
Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
出版信息
Adv Exp Med Biol. 2010;703:151-62. doi: 10.1007/978-1-4419-5635-4_11.
The effect of complement depletion with humanized cobra venom factor (CVF) on retinal lesion development/neovascularization was determined in a mouse model of wet age-related macular degeneration (AMD). Mice were treated with the humanized CVF protein HC3-1496 prior to, and once daily for 28 days after laser coagulation surgery of the retina. CVF transgenic mice exhibiting permanently low levels of serum complement activity and PBS-treated mice served as positive and negative controls, respectively. Fluorescein isothiocyanate (FITC)-dextran funduscopy after laser surgery indicated the presence of lesions in all mice that underwent laser surgery. In HC3-1496-treated mice as well as CVF transgenic mice smaller lesions were seen after 8 days. Measurement of lesion sizes by histopathological examination of eyes after 28 days revealed a significant reduction of lesion area and volume in both HC3-1496-treated animals and CVF transgenic animals compared to PBS-treated control animals. Systemic complement depletion with a complement depletor, such as the humanized CVF protein HC3-1496, represents a promising therapeutic concept for patients with wet AMD.
采用人源化眼镜蛇蛇毒因子（CVF）耗尽补体的方法，观察其对湿性年龄相关性黄斑变性（AMD）小鼠模型中视网膜病变/新生血管形成的影响。在视网膜激光凝固手术后，用 HC3-1496 蛋白对小鼠进行预处理，并每日治疗一次，共 28 天。CVF 转基因小鼠表现出血清补体活性持续降低，PBS 处理的小鼠分别作为阳性和阴性对照。激光手术后的荧光素异硫氰酸酯（FITC）-葡聚糖眼底镜检查显示，所有接受激光手术的小鼠均出现病变。在 HC3-1496 治疗组和 CVF 转基因小鼠中，在 8 天后可观察到较小的病变。28 天后通过对眼部进行组织病理学检查来测量病变大小，与 PBS 处理的对照组相比，HC3-1496 治疗组和 CVF 转基因组的病变面积和体积均显著减少。用补体耗竭剂（如人源化 CVF 蛋白 HC3-1496）进行全身性补体耗竭，为湿性 AMD 患者提供了一种有前途的治疗概念。
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