Retinal Function and Structure in the Hypotransferrinemic Mouse
| Autor: | Alexey Obolensky, Eyal Banin, Michal Lederman, Itay Chowers, Michelle Grunin |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Retinal degeneration
medicine.medical_specialty Pathology Iron Biology Real-Time Polymerase Chain Reaction Retina Mice chemistry.chemical_compound Internal medicine Gene expression Electroretinography medicine Animals RNA Messenger chemistry.chemical_classification Mice Inbred BALB C Anemia Iron-Deficiency medicine.diagnostic_test Retinal Degeneration Transferrin Retinal medicine.disease Immunohistochemistry Ophthalmoscopy Disease Models Animal Oxidative Stress medicine.anatomical_structure Endocrinology Gene Expression Regulation chemistry biology.protein Ceruloplasmin Immunostaining |
| Zdroj: | Investigative Opthalmology & Visual Science. 53:605 |
| ISSN: | 1552-5783 |
| Popis: | PURPOSE The iron carrier transferrin is expressed at remarkably high levels in normal retinas and is upregulated during retinal degeneration. The authors characterized the consequences of genetically reduced retinal transferrin production on retinal structure and function. METHODS Hypotransferrinemic (HPX⁻/⁻) mice treated with weekly intraperitoneal salvage transferrin injections were examined at 1 and 2 months of age. HPX⁻/⁻, HPX⁺/⁻, and wild-type (WT) mice were evaluated by electroretinography, ophthalmoscopy, and histology. Retinal iron content and transferrin levels were measured. RNA levels of genes involved in iron homeostasis and antioxidative response were determined by quantitative PCR. Oxidative injury was assessed by immunostaining for 4-hydroxy-2-nonenal (HNE). RESULTS At 2 months, dark-adapted, mixed rod-cone response b-wave amplitudes were significantly lower in HPX⁻/⁻ mice than in WT mice (340 ± 112 μV vs. 624 ± 134 μV [mean ± SEM]; P = 0.002). Oscillatory potentials were significantly suppressed in HPX mice, and ophthalmoscopy demonstrated marked retinal pallor. Quantitative immunostaining revealed a 39% reduction of transferrin content in HPX⁻/⁻ compared with WT retinas (P = 0.01). mRNA levels of Tf, Tf receptor, and ceruloplasmin were decreased, whereas mRNA for antioxidant genes were elevated in HPX⁻/⁻ retinas. HNE staining was reduced in mice carrying the mutant HPX allele. Histologic examination demonstrated preserved retinal structure, and retinal iron content was similar across the strains. CONCLUSIONS Despite the lack of wild-type retinal transferrin production and low levels of retinal transferrin protein, the retinal morphology and retinal iron content in HPX⁻/⁻ mice treated by systemic salvage transferrin injections are normal until age 2 months. However, retinal function and gene expression of some of the iron-associated genes are significantly altered. |
| Databáze: | OpenAIRE |
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