Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah, United States Department of Neurobiology and Anatomy, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
Invest Ophthalmol Vis Sci. 2014 May 22;55(6):3842-50. doi: 10.1167/iovs.13-13111.
Polypoidal choroidal vasculopathy (PCV) is characterized by a branching vascular network (BVN) of choroid that terminates in polypoidal dilations. We have previously reported the generation of the first PCV model by transgenically expressing human HTRA1 (hHTRA1(+)), a multifunctional serine protease, in mouse RPE. The purpose of this study was to perform a comprehensive examination of the PCV phenotypes (e.g., lesion type and distribution) of hHTRA1(+) mice by a variety of in vivo imaging techniques.
We generated improved hHTRA1(+) mice with a more consistent phenotype. Transgenic mice were examined by indocyanine green angiography (ICGA), fluorescein angiography, funduscopy, and spectral-domain optical coherence tomography. In particular, we performed ICGA by tail vein injection of ICG to obtain high-quality ICGA comparable to human studies in terms of the three phases (early, middle, and late) of angiography.
The polyps can be detected in the early "fill-in" phase of ICGA, and most lesions become visible in the middle phase and are more distinct in the late phase with the fading of surrounding vessels. In addition to the two key features of PCV (polypoidal dilations and BVNs), hHTRA1(+) mice exhibit other features of PCV (i.e., late geographic hyperfluorescence, pigment epithelial detachment, and hyperfluorescent plaque). Polypoidal lesions appear as reddish orange nodules on funduscopy.
Transgenic hHTRA1(+) mice exhibit a rich spectrum of "clinical" features that closely mimic human PCV. This animal model will serve as an invaluable tool for future mechanistic and translational studies of PCV and other forms of choroidal vasculopathies.
息肉样脉络膜血管病变（PCV）的特征是脉络膜分支血管网络（BVN）终止于息肉样扩张。我们之前报道过通过在小鼠 RPE 中转基因表达多功能丝氨酸蛋白酶人 HTRA1（hHTRA1(+））生成首个 PCV 模型。本研究的目的是通过各种体内成像技术对 hHTRA1(+) 小鼠的 PCV 表型（例如病变类型和分布）进行全面检查。
我们生成了具有更一致表型的改良 hHTRA1(+) 小鼠。通过吲哚菁绿血管造影（ICGA）、荧光素血管造影、眼底镜检查和光谱域光相干断层扫描检查转基 因小鼠。特别是，我们通过尾静脉注射 ICG 进行 ICGA，以获得与人类研究在三个阶段（早期、中期和晚期）相媲美的高质量 ICGA。
在 ICGA 的早期“填充”阶段可以检测到息肉，大多数病变在中期变得可见，并且在晚期随着周围血管的褪色变得更加明显。除了 PCV 的两个关键特征（息肉样扩张和 BVN）外，hHTRA1(+) 小鼠还表现出 PCV 的其他特征（即晚期地理高荧光、色素上皮脱离和高荧光斑块）。息肉样病变在眼底镜检查中呈现出红橙色结节。
转基 因 hHTRA1(+) 小鼠表现出丰富的“临床”特征，与人类 PCV 非常相似。这种动物模型将成为未来 PCV 和其他形式脉络膜血管病变的机制和转化研究的宝贵工具。
