Amany Tawfik1, Jaya P Gnana-Prakasam2, Sylvia B Smith1, Vadivel Ganapathy2. 1. Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States James & Jean Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States. 2. James & Jean Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States.
Abstract
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 Müller 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 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. 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 Müller cells and microglia. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
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 Müller 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 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. 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 Müller cells and microglia. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Lan G Coffman; Derek Parsonage; Ralph D'Agostino; Frank M Torti; Suzy V Torti Journal: Proc Natl Acad Sci U S A Date: 2009-01-06 Impact factor: 11.205
Authors: Xining He; Paul Hahn; Jared Iacovelli; Robert Wong; Chih King; Robert Bhisitkul; Mina Massaro-Giordano; Joshua L Dunaief Journal: Prog Retin Eye Res Date: 2007-08-11 Impact factor: 21.198
Authors: Jaya P Gnana-Prakasam; Pamela M Martin; Barbara A Mysona; Penny Roon; Sylvia B Smith; Vadivel Ganapathy Journal: Biochem J Date: 2008-04-01 Impact factor: 3.857
Authors: Christian Siebold; Toshihide Yamashita; Philippe P Monnier; Bernhard K Mueller; R Jeroen Pasterkamp Journal: Trends Cell Biol Date: 2016-12-19 Impact factor: 20.808