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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.
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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.
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).
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.
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.
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