May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Retinal Function and Structure in the Hypotransferrinemic (HPX) Mouse
Author Affiliations & Notes
  • I. Chowers
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • M. Lederman
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
    Biochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel
  • A. Obolenskey
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
    Biochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel
  • E. Banin
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • M. Chevion
    Biochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel
  • Footnotes
    Commercial Relationships  I. Chowers, None; M. Lederman, None; A. Obolenskey, None; E. Banin, None; M. Chevion, None.
  • Footnotes
    Support  BSF
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3440. doi:https://doi.org/
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    • Get Citation

      I. Chowers, M. Lederman, A. Obolenskey, E. Banin, M. Chevion; Retinal Function and Structure in the Hypotransferrinemic (HPX) Mouse. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3440. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The iron carrier transferrin is expressed at remarkably high levels in the normal retina, and its expression is further up-regulated in Age Related Macular Degeneration (AMD). The role of transferrin in AMD and other retinal degenerations is still unclear. A point mutation in the transferrin gene of HPX mice results in less than 1% of normal transferrin protein production. We aimed to characterize the retinal phenotype of HPX mice in order to gain additional insight into the role of transferrin in retinal function.

Methods: : To ensure their survival, HPX-/- mice were treated weekly with intraperitoneal injections of transferrin. Electroretinograms (ERGs) were recorded at one and two months of age in HPX-/-, HPX-/+, and wild type (WT) mice. At the two months time point ophthalmoscopy was performed, retinal structure was evaluated by histology, and transferrin content was estimated by semi-quantitative immunohistochemistry (IHC). mRNA levels of transferrin, ceruloplasmin, and transferrin receptor were measured by quantitative PCR (QPCR).

Results: : At one and two months of age WT and HPX+/- mice had similar dark- and light-adapted full-field ERG responses whereas in HPX-/- mice ERG amplitudes were significantly reduced. For example, at two months of age, mean dark-adapted mixed cone-rod b-wave amplitude at maximal stimulus intensity was 357±123µV in HPX-/-, versus 624±134µV in WT mice (p=0.01). Ophthalmoscopy revealed retinal pallor in HPX-/- mice. However, histological examination demonstrated preserved retinal structure and total retinal thickness did not differ between the three groups of animals (WT: 192±8.5µm, HPX+/-: 200±7µm, HPX-/-: 197±15µm, p=0.63). IHC for transferrin demonstrated reduced staining intensity by a mean of 17% (p=0.3) and 37% (p=0.03) in HPX+/- retinas and HPX-/- retinas, respectively, as compared with WT retinas. QPCR demonstrated decreased mRNA levels of transferrin (by 2.7 folds; p =0.03), ceruloplasmin (by 1.6-fold; p=0.05), and transferrin receptor (by 2.2-fold; p=0.003) in HPX-/- mice compared with WT mice.

Conclusions: : Despite the lack of retinal transferrin protein production, systemic transferrin supplementation enables postnatal retinal development in HPX-/- mice. Yet, ERG responses and retinal transferrin protein levels are altered in HPX-/- mice, suggesting that transferrin may be required for normal retinal function.

Keywords: retina • oxidation/oxidative or free radical damage • gene/expression 
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