Deletion of Hemojuvelin, an Iron-Regulatory Protein, in Mice Results in Abnormal Angiogenesis and Vasculogenesis in Retina Along With Reactive Gliosis

作者：Tawfik Amany; Gnana Prakasam Jaya P; Smith Sylvia B; Ganapathy Vadivel^*

来源：Investigative Ophthalmology & Visual Science, 2014, 55(6): 3616-3625.

DOI：10.1167/iovs.13-13677

• iron
• angiogenesis
• retinal vasculature
• gliosis

PURPOSE. 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.
METHODS. 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 Muller cells and microglia.
RESULTS. 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 Muller 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.
CONCLUSIONS. 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 Muller cells and microglia.

• 出版日期2014-6