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Alex Jones, Sandeep Kumar, Shixian Wang, Zachary Berriochoa, Yingbin Fu; Histopathological characterization of different lesion types of polypoidal choroidal vasculopathy in HTRA1 transgenic mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1184.
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© ARVO (1962-2015); The Authors (2016-present)
Polypoidal choroidal vasculopathy (PCV) is characterized by a branching vascular network (BVN) with terminal polypoidal dilations (polyps) in the choroid. The etiology and pathogenesis of PCV are largely unknown. We recently generated the first PCV model by transgenically expressing human HTRA1 in mouse retinal pigment epithelium (RPE). By in vivo imaging, HTRA1 mice exhibit a number of angiographic features that are associated with PCV (e.g. polyps ,BVN, pigment epithelium detachment (PED), late geographic hyperfluorescence (LGH)). This PCV model provides an unprecedented opportunity to correlate phenotypes charaterized by in vivo imaging with the correspoding histopathological features. Our purpose is to understand the pathogenesis of different types of lesions and their progression.
HTRA1 mice were injected with a mixture of FITC-dextran and indocyanine green (ICG). Guided by ICG angiography (ICGA), fluorescein angiography and flatmount-fluorescent microscopy, we surgically excised different types of lesions. The excised lesion-containing tissues were fixed overnight and resin-embedded. Thin plastic sections (1um) were stained with Richardson’s stain.
The small-polyp lesion shows a cluster of dilated thin-wall vessels with broken vessel walls, which “pushes” RPE and retinal layers upward. A small PED is observed above the thin-wall vessel. The large PCV lesion with polyps and BVN is associated with extensive exudation of plasma proteins. The artery wall is thick and hyalinized, which obstructs the vessel. The large PCV lesion causes extensive RPE degeneration accompanied by photoreceptor degeneration. In contrast, the small PCV lesion causes milder RPE degeneration with no obvious signs of photoreceptor degeneration. This may explain why PCV patients with larger lesions have higher rates of lesion progression and severe complications. The LGH lesion contains both dilated-thin broken vessels, which presses into the RPE and photoreceptor, and hyalinized vessels. RPE vacuoles are detected while photoreceptors are mostly intact. Macrophages and neutrophils were present in both large PCV lesion and LGH.
PCV is the result of degenerative changes of choroidal vessels triggered by the proteolytic activity of HTRA1. The presence of inflammatory cells in large lesions suggests inflammatory processes are involved in the progression of PCV.
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