Iron-mediated retinal degeneration in haemojuvelin-knockout mice

Jaya P. Gnana-Prakasam, Amany Tawfik, Michelle Romej, Sudha Ananth, Pamela M. Martin, Sylvia B. Smith, Vadivel Ganapathy

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins HFE (human leucocyte antigen-like protein involved in iron homoeostasis), transferrin receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Recent studies have established the expression of all of the five genes in the retina, indicating their importance in retinal iron homoeostasis. Previously, we demonstrated that HJV is expressed in RPE (retinal pigment epithelium), the outer and inner nuclear layers and the ganglion cell layer. In the present paper, we report on the consequences of Hjv deletion on the retina in mice. Hjv -/-mice at ≥18 months of age had increased iron accumulation in the retina with marked morphological damage compared with age-matched controls; these changes were not found in younger mice. The retinal phenotype in Hjv -/- mice included hyperplasia of RPE. We isolated RPE cells from wild-type and Hjv -/- mice and examined their growth patterns. Hjv -/-RPE cells were less senescent and exhibited a hyperproliferative phenotype. Hjv -/- RPE cells also showed up-regulation of Slc7a11 (solute carrier family 7 member 11 gene), which encodes the 'transporter proper' subunit xCT in the heterodimeric amino acid transporter xCT/4F2hc (cystine/glutamate exchanger). BMP6 (bone morphogenetic protein 6) could not induce hepcidin expression in Hjv -/- RPE cells, confirming that retinal cells require HJV for induction of hepcidin via BMP6 signalling. HJV is a glycosylphosphatidylinositol-anchored protein, and the membrane-associated HJV is necessary for BMP6-mediated activation of hepcidin promoter inRPE cells. Taken together, these results confirm the biological importance of HJV in the regulation of iron homoeostasis in the retina and in RPE.

Original languageEnglish (US)
Pages (from-to)599-608
Number of pages10
JournalBiochemical Journal
Issue number2
StatePublished - Jan 15 2012


  • Bone morphogenetic protein (BMP)
  • Haemochromatosis
  • Haemojuvelin (HJV)
  • Hepcidin
  • Knockout mouse
  • Retinal pigment epithelium (RPE)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Iron-mediated retinal degeneration in haemojuvelin-knockout mice'. Together they form a unique fingerprint.

Cite this