Deletion of hemojuvelin, an iron-regulatory protein, in mice results in abnormal angiogenesis and vasculogenesis in retina along with reactive gliosis

Amany Mohamed Tawfik, Jaya Pranava Gnana-Prakasam, Sylvia B Smith, Vadivel Ganapathy

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3616-3625
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number6
DOIs
StatePublished - May 8 2014

Fingerprint

Iron-Regulatory Proteins
Gliosis
Retina
Blood Vessels
Microglia
Occludin
Tight Junction Proteins
Iron Overload
Fluorescein Angiography
Glial Fibrillary Acidic Protein
Vimentin
Lectins
Trypsin
Vascular Endothelial Growth Factor A
Collagen
Iron

Keywords

  • Angiogenesis
  • Gliosis
  • Iron
  • Retinal vasculature

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

@article{6faf4f8455834bdebf9944f4ab96312a,
title = "Deletion of hemojuvelin, an iron-regulatory protein, in mice results in abnormal angiogenesis and vasculogenesis in retina along with reactive gliosis",
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 M{\"u}ller 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 M{\"u}ller 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 M{\"u}ller cells and microglia.",
keywords = "Angiogenesis, Gliosis, Iron, Retinal vasculature",
author = "Tawfik, {Amany Mohamed} and Gnana-Prakasam, {Jaya Pranava} and Smith, {Sylvia B} and Vadivel Ganapathy",
year = "2014",
month = "5",
day = "8",
doi = "10.1167/iovs.13-13677",
language = "English (US)",
volume = "55",
pages = "3616--3625",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "6",

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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 Mohamed

AU - Gnana-Prakasam, Jaya Pranava

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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