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Amany Tawfik, Jaya P. Gnana-Prakasam, Sylvia B. Smith, Vadivel Ganapathy; Deletion of Hemojuvelin, an Iron-Regulatory Protein, in Mice Results in Abnormal Angiogenesis and Vasculogenesis in Retina Along With Reactive Gliosis. Invest. Ophthalmol. Vis. Sci. 2014;55(6):3616-3625. doi: https://doi.org/10.1167/iovs.13-13677.
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Loss-of-function mutations in hemojuvelin (HJV) cause juvenile hemochromatosis, an iron-overload disease. Deletion of Hjv in mice results in excessive iron accumulation and morphologic changes in the retina. Here, we studied the retinal vasculature in Hjv−/− mice.
Age-matched wild-type and Hjv−/− mice were used for fluorescein angiography and preparation of retinal cryosections, flat-mounts, and trypsin-digested blood vessels. Retinal angiogenesis was monitored by immunofluorescent detection of isolectin-B4, endoglin, and VEGF. Retinal vasculogenesis was monitored by immunofluorescent detection of collagen IV. Reactive gliosis was assessed based on the expression of glial fibrillary acidic protein and vimentin and CD11b/c as markers for Müller cells and microglia.
Between 18 and 24 months of age, retinas of Hjv−/− mice displayed marked disruptions in angiogenesis and vasculogenesis. Blood vessels in Hjv−/− mice were tortuous and dilated, with a decrease in the tight-junction protein occludin. There was also evidence of neovascularization in Hjv−/− mice with blood vessels appearing in the vitreous, which were leaky. There was reactive gliosis in these mice involving both Müller cells and microglia. Such changes were not detected at 2 weeks of age. Even at the age of 4 months, retinas of Hjv−/− mice were almost normal with changes just beginning to appear. Thus, the vascular changes in Hjv−/− mouse retinas represent an age-dependent phenomenon.
Deletion of Hjv in mice leads to abnormal retinal angiogenesis/vasculogenesis, with proliferation of new, leaky blood vessels in the vitreous. These changes are accompanied with reactive gliosis involving Müller cells and microglia.
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