TY - JOUR
T1 - Deletion of hemojuvelin, an iron-regulatory protein, in mice results in abnormal angiogenesis and vasculogenesis in retina along with reactive gliosis
AU - Tawfik, Amany
AU - Gnana-Prakasam, Jaya P.
AU - Smith, Sylvia B.
AU - Ganapathy, Vadivel
PY - 2014/5/8
Y1 - 2014/5/8
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Gliosis
KW - Iron
KW - Retinal vasculature
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UR - http://www.scopus.com/inward/citedby.url?scp=84902449592&partnerID=8YFLogxK
U2 - 10.1167/iovs.13-13677
DO - 10.1167/iovs.13-13677
M3 - Article
C2 - 24812553
AN - SCOPUS:84902449592
SN - 0146-0404
VL - 55
SP - 3616
EP - 3625
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 6
ER -