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

Amany Tawfik, Jaya P. Gnana-Prakasam, Sylvia B. Smith, Vadivel Ganapathy

Research output: Contribution to journalArticle

8 Scopus citations

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
Publication statusPublished - May 8 2014

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Keywords

  • Angiogenesis
  • Gliosis
  • Iron
  • Retinal vasculature

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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