Haemochromatosis is a
genetic disorder of
iron overload resulting from loss-of-function mutations in genes coding for the
iron-regulatory proteins HFE [HLA-like
protein involved in
iron (Fe) homoeostasis],
transferrin receptor 2,
ferroportin,
hepcidin and HJV (haemojuvelin). Expression of the first four genes coding for these
proteins in retina has been established. Here we report on the expression of HJV. Since
infection of retina with CMV (cytomegalovirus) causes
blindness, we also investigated the expression of HJV and other
iron-regulatory proteins in retina during CMV
infection. HJV (HJV gene)
mRNA was expressed in RPE (retinal pigment epithelium)/eyecup and neural retina in mouse. In situ hybridization and immunohistochemistry confirmed the presence of HJV
mRNA and
protein in RPE, outer and inner nuclear layers, and
ganglion cell layer. Immunocytochemistry with cell lines and primary cell cultures showed HJV expression in RPE and Müller cells. In RPE, the expression was restricted to apical membrane.
Infection of primary cultures of mouse RPE with CMV increased HJV
mRNA and
protein levels. Under similar conditions, HFE (HFE gene)
mRNA levels were not altered, but
HFE protein was decreased.
Hepcidin expression was, however, not altered. These findings were demonstrable in vivo with CMV-infected mouse retina. The CMV-induced up-regulation of HJV in RPE was independent of changes in HFE because the phenomenon was also seen in HFE-null RPE cells. CMV-infected primary RPE cells showed evidence of
iron accumulation and oxidative stress, as indicated by increased levels of
ferritin and hydroxynonenal. The observed changes in HJV expression and
iron status during CMV
infection in retina may have significance in the pathophysiology of CMV
retinitis.