Skip to main content

Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice.

Publication ,  Journal Article
Hadziahmetovic, M; Song, Y; Ponnuru, P; Iacovelli, J; Hunter, A; Haddad, N; Beard, J; Connor, JR; Vaulont, S; Dunaief, JL
Published in: Invest Ophthalmol Vis Sci
January 5, 2011

PURPOSE: Iron dysregulation can cause retinal disease, yet retinal iron regulatory mechanisms are incompletely understood. The peptide hormone hepcidin (Hepc) limits iron uptake from the intestine by triggering degradation of the iron transporter ferroportin (Fpn). Given that Hepc is expressed in the retina and Fpn is expressed in cells constituting the blood-retinal barrier, the authors tested whether the retina may produce Hepc to limit retinal iron import. METHODS: Retinas of Hepc(-/-) mice were analyzed by histology, autofluorescence spectral analysis, atomic absorption spectrophotometry, Perls' iron stain, and immunofluorescence to assess iron-handling proteins. Retinal Hepc mRNA was evaluated through qPCR after intravitreal iron injection. Mechanisms of retinal Hepc upregulation were tested by Western blot analysis. A retinal capillary endothelial cell culture system was used to assess the effect of exogenous Hepc on Fpn. RESULTS: Hepc(-/-) mice experienced age-dependent increases in retinal iron followed by retinal degeneration with autofluorescent RPE, photoreceptor death, and subretinal neovascularization. Hepc(-/-) mice had increased Fpn immunoreactivity in vascular endothelial cells. Conversely, in cultured retinal capillary endothelial cells, exogenous Hepc decreased both Fpn levels and iron transport. The retina can sense increased iron levels, upregulating Hepc after phosphorylation of extracellular signal regulated kinases. CONCLUSIONS: These findings indicate that Hepc is essential for retinal iron regulation. In the absence of Hepc, retinal degeneration occurs. Increases in Hepc mRNA levels after intravitreal iron injection combined with Hepc-mediated decreases in iron export from cultured retinal capillary endothelial cells suggest that the retina may use Hepc for its tissue-specific iron regulation.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

January 5, 2011

Volume

52

Issue

1

Start / End Page

109 / 118

Location

United States

Related Subject Headings

  • Spectrophotometry, Atomic
  • Retinal Pigment Epithelium
  • Retinal Degeneration
  • Retina
  • Receptors, Transferrin
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Ophthalmology & Optometry
  • Mice, Knockout
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hadziahmetovic, M., Song, Y., Ponnuru, P., Iacovelli, J., Hunter, A., Haddad, N., … Dunaief, J. L. (2011). Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice. Invest Ophthalmol Vis Sci, 52(1), 109–118. https://doi.org/10.1167/iovs.10-6113
Hadziahmetovic, Majda, Ying Song, Padmavathi Ponnuru, Jared Iacovelli, Allan Hunter, Nadine Haddad, John Beard, James R. Connor, Sophie Vaulont, and Joshua L. Dunaief. “Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice.Invest Ophthalmol Vis Sci 52, no. 1 (January 5, 2011): 109–18. https://doi.org/10.1167/iovs.10-6113.
Hadziahmetovic M, Song Y, Ponnuru P, Iacovelli J, Hunter A, Haddad N, et al. Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice. Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):109–18.
Hadziahmetovic, Majda, et al. “Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice.Invest Ophthalmol Vis Sci, vol. 52, no. 1, Jan. 2011, pp. 109–18. Pubmed, doi:10.1167/iovs.10-6113.
Hadziahmetovic M, Song Y, Ponnuru P, Iacovelli J, Hunter A, Haddad N, Beard J, Connor JR, Vaulont S, Dunaief JL. Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice. Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):109–118.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

January 5, 2011

Volume

52

Issue

1

Start / End Page

109 / 118

Location

United States

Related Subject Headings

  • Spectrophotometry, Atomic
  • Retinal Pigment Epithelium
  • Retinal Degeneration
  • Retina
  • Receptors, Transferrin
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Ophthalmology & Optometry
  • Mice, Knockout
  • Mice, Inbred C57BL