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(Investigative Ophthalmology and Visual Science. 2006;47:4238-4244.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0026
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Expression and Polarized Localization of the Hemochromatosis Gene Product HFE in Retinal Pigment Epithelium

Pamela M. Martin,1 Jaya P. Gnana-Prakasam,1 Penny Roon,2 Robert G. Smith,3 Sylvia B. Smith,2 and Vadivel Ganapathy1

1From the Departments of Biochemistry and Molecular Biology and 2Cellular Biology and Anatomy, and the 3Synapses and Cognitive Neuroscience Center, Medical College of Georgia, Augusta, Georgia.

PURPOSE. Hereditary hemochromatosis is an autosomal recessive disorder of iron overload leading to oxidative stress. Mutations in HFE are responsible for ~90% of cases of this disease. HFE is the principal regulator of iron homeostasis, and the process involves interaction with transferrin receptor (TfR)-1, transferrin receptor (TfR)-2, and ß2-microglobulin (ß2M). Expression of HFE has not been investigated in the retina. In the present study, the expression of HFE and the HFE-interacting proteins TfR1, TfR2, and ß2M were analyzed in mouse retina.

METHODS. RT-PCR was used to detect the expression of HFE mRNA in neural retina and the RPE-eyecup. Expression of HFE in intact retina was investigated by in situ hybridization, immunofluorescence, and immunogold electron microscopy. Expression of HFE-interacting proteins was also analyzed using similar techniques.

RESULTS. RT-PCR showed predominant expression of HFE mRNA in the RPE-eyecup. In situ hybridization in intact retina revealed that HFE mRNA is expressed almost exclusively in RPE Immunofluorescence and immunogold electron microscopy showed that HFE protein was specifically associated with the basolateral membrane of RPE. Expression of the HFE-interacting proteins TfR1, TfR2, and ß2M was also evident in the retina.

CONCLUSIONS. This is the first report on the expression of HFE in the retina. The specific localization of HFE and its interacting proteins, TfR1 and TfR2, at the basolateral membrane of RPE is relevant to the regulation of iron homeostasis in this cell. Patients with hemochromatosis may have impairment of iron homeostasis in RPE, potentially contributing to age-related RPE dysfunction and retinal degeneration.




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P. M. Martin, Y. Dun, B. Mysona, S. Ananth, P. Roon, S. B. Smith, and V. Ganapathy
Expression of the Sodium-Coupled Monocarboxylate Transporters SMCT1 (SLC5A8) and SMCT2 (SLC5A12) in Retina
Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3356 - 3363.
[Abstract] [Full Text] [PDF]


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