Abstract | PURPOSE: METHODS: We generated double mutant mice by combining the Cep290(rd16) and Rkip(ko) alleles (Cep290(rd16):Rkip(+/ko) and Cep290(rd16):Rkip(ko/ko)). Retinal function was assessed by ERG and retinal morphology and protein trafficking were assessed by histology, transmission electron microscopy (TEM), and immunofluorescence analysis. Cell death was examined by apoptosis. RESULTS: Prior to testing our hypothesis, we examined ERG and retinal morphology of Rkip(ko/ko) mice and did not find any detectable differences compared with wild-type mice. The Cep290(rd16):Rkip(+/ko) mice exhibited similar retinopathy as Cep290(rd16); however, Cep290(rd16): Rkip(ko/ko) double knockout mice demonstrated a substantial improvement (>9-fold) in photoreceptor function and structure at P18 as of Cep290(rd16) mice. We consistently detected transient preservation of photoreceptors at P18 and polarized trafficking of opsins to sensory cilia in the double mutant mice; however, retinal degeneration ensued by P30. CONCLUSIONS: Our studies implicate CEP290-RKIP pathway in CEP290-retinal degeneration and suggest that targeting RKIP levels can delay photoreceptor degeneration, assisting in extending the time-window for treating such rapidly progressing blindness disorder.
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Authors | Balajikarthick Subramanian, Manisha Anand, Naheed W Khan, Hemant Khanna |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 55
Issue 9
Pg. 5788-94
(Aug 14 2014)
ISSN: 1552-5783 [Electronic] United States |
PMID | 25125607
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. |
Chemical References |
- Antigens, Neoplasm
- Cell Cycle Proteins
- Cep290 protein, mouse
- Cytoskeletal Proteins
- Nuclear Proteins
- Opsins
- PEBP1 protein, human
- Phosphatidylethanolamine Binding Protein
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Topics |
- Analysis of Variance
- Animals
- Antigens, Neoplasm
- Apoptosis
(physiology)
- Cell Cycle Proteins
- Ciliary Body
(metabolism)
- Cytoskeletal Proteins
- Disease Models, Animal
- Electroretinography
- Mice
- Mice, Knockout
- Nuclear Proteins
- Opsins
(metabolism)
- Phosphatidylethanolamine Binding Protein
(deficiency, physiology)
- Photoreceptor Cells, Vertebrate
(physiology)
- Retinal Degeneration
(pathology, physiopathology)
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