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Michael Hung Ngo, johanna borowska, sara nejat, Melanie Kelly, Chris McMaster, Johane M Robitaille, ; FZD4 haploinsufficiency delays recovery of retinopathy in the ocular ischemic retinopathy (OIR) mouse model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3400.
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Genes in the Norrin-FZD4 signaling pathway have been implicated as risk factors for the development of severe retinopathy of prematurity (ROP). In this study, we measure the effects of FZD4 haploinsufficiency on the course of retinopathy in a Fzd4 mouse model using a modified ocular ischemic retinopathy (OIR) protocol.
The development and recovery of retinopathy in B6;129-Fzd4tm1Nat/J mice was compared to wild-type mice (C57BL/6J) at P12, P17 and P25. Retinas harvested at each time point were stained with conjugated lectin to visualize the endothelium. Flat mounted retinas were imaged, and the avascular and total areas were quantified using Image J software with the NV_Swift plugin. Vessel count and structure were quantitatively analyzed and compared in the areas that remained vascularized in the periphery and in the central area following revascularization.
A significant delay in revascularization was detected at P17 in the heterozygous Fzd4 mice compared to wild-type. The delay in revascularization recovered by P25. No difference was measured in maximum vaso-obliteration at P12 or maximum neovascularization at P17. No difference in the vessel count or structure was found.
FZD4 haploinsufficiency causes a delay in revascularization of vaso-obliterated retina in this modified OIR mouse model. This supports previous studies demonstrating an association between rare polymorphisms/mutations in genes in this pathway and severe ROP, and suggests a possible mechanism for increasing the risk of severe ROP in humans by lengthening the period during which complications from ROP can occur.<br />
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