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Sandeep Kumar, Zachary Berriochoa, Alex Jones, Yingbin Fu; Angiographic features of transgenic mice with increased expression of human serine protease HTRA1 in retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5237.
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Polypoidal choroidal vasculopathy (PCV) is characterized by branching vascular network (BVN) with terminal polypoidal dilations (polyps) in choroid. Previously, we reported the generation of the first PCV model by transgenically expressing human HTRA1 in mouse retinal pigment epithelium. Here, we performed comprehensive examinations on PCV phenotypes (e.g. lesion type, distribution) of HTRA1 mice by a variety of in vivo imaging techniques. Especially, we have applied the technique of Indocyanine Green Angiography via tail-vein injection (IV-ICGA) to mouse models for the first time to obtain high quality ICGA comparable to human studies in terms of the three phases (early, middle, and late) of angiography.
We compared the influence of delivery route (Intraperitoneal injection (IP) vs. IV, >100 mice for each method) and mouse coat color (albino vs. pigmented) on ICGA using HTRA1 and WT mice. 125 HTRA1 mice (1-14 months) and 55 wild-type littermate controls were examined by IV-ICGA, fluorescein angiography, funduscopy, and spectral-domain optical coherence tomography (SD-OCT).
Our data suggest that, 1) IV-ICGA is superior to IP (or subcutaneous (SC))-ICGA that are currently used in animal research for characterizing lesions in the choroid; 2) ICGA performed on albino mice gives clearer pictures of choroidal vessels than that performed on pigmented mice. On IV-ICGA, the two key features of PCV (BVN and polyps) are present in 118 HTRA1 mice (out of 125). Polyps can be detected in the early “fill-in” phase of ICGA, most lesions become visible in the middle phase and become more distinct in the late phase with the fading of surrounding vessels. HTRA1 mice exhibit additional features of PCV such as late geographic hyperfluorescence, pigment epithelium detachment, and hyperfluorescent plaque. On funduscopy, polypoidal lesions appear as reddish orange nodules. SD-OCT located lesions in the choroid and round protrusions of the RPE underneath the polyps. These phenotypes share remarkable similarities to the well established clinical features of human PCV. Currently, no other animal models exist with these features.
HTRA1 mice exhibit a rich spectrum of “clinical” features that closely mimic human PCV, making it an invaluable tool for future mechanistic and translational studies of this disease and other forms of choroidal vasculopathies.
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