Abstract | PURPOSE: METHODS: We constructed Prom1 knockout mice with two distinct genetic backgrounds of C57BL/6 and C57BL/6xCBA/NSlc, and investigated the photoreceptor degeneration by means of histology and functional tests.. In addition, we examined the effect of light on the Prom1(-/-) retina by rearing the mice in the normal light/dark cycle and completely dark conditions. Finally, we investigated if the retinoic-acid derivative Fenretinide slowed the pace of retinal degeneration in these mouse models. RESULTS: The Prom1(-/-)-knockout mice with both backgrounds developed photoreceptor degeneration after eye opening, but the CB57/BL6-background mice developed photoreceptor cell degeneration much faster than the C57BL/6xCBA/NSlc mice, demonstrating genetic background dependency.. Interestingly, our histologic and functional examination showed that the photoreceptor cell degeneration of Prom1-knockout mice was light-dependent, and was almost completely inhibited when the mutant mice were kept in the dark. The Prom1-knockout retina showed strong downregulation of expression of the visual cycle components, Rdh12 and Abca4. Furthermore, administration of Fenretinide, which lowers the level of the toxic lipofuscin, slowed the degeneration of photoreceptor cells. CONCLUSIONS: These findings improve our understanding of the mechanism of cell death in Prominin-1-related disease and provide evidence that fenretinide may be worth studying in human disease.
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Authors | Margaret Dellett, Noriaki Sasai, Kenji Nishide, Silke Becker, Vasiliki Papadaki, G Astrid Limb, Anthony T Moore, Toru Kondo, Shin-Ichi Ohnuma |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 56
Issue 1
Pg. 164-76
(Nov 20 2014)
ISSN: 1552-5783 [Electronic] United States |
PMID | 25414197
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc. |
Chemical References |
- AC133 Antigen
- Antigens, CD
- Glycoproteins
- PROM1 protein, human
- Peptides
- Prom1 protein, mouse
- DNA
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Topics |
- AC133 Antigen
- Animals
- Antigens, CD
(genetics, metabolism)
- DNA
(genetics)
- DNA Mutational Analysis
- Disease Models, Animal
- Electroretinography
- Glycoproteins
(genetics, metabolism)
- Immunohistochemistry
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microscopy, Electron
- Mutation
- Peptides
(genetics, metabolism)
- Photic Stimulation
- Photoreceptor Cells, Vertebrate
(metabolism, ultrastructure)
- Real-Time Polymerase Chain Reaction
- Retinal Degeneration
(genetics, metabolism, physiopathology)
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