| Neovascularization, enhanced inflammatory response, and age-related cone dystrophy in the Nrl-/-Grk1-/- mouse retina. | |
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MedLine Citation:
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PMID: 20688726 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The effects of aging and light exposure on cone photoreceptor survival were compared between mouse retinas of neural retina leucine zipper knockout (Nrl(-/-)) mice and double-knockout mice lacking G-protein-coupled receptor kinase 1 (Nrl(-/-)Grk1(-/-)). METHODS: Mice were reared in total darkness, ambient cyclic light, or constant light, and their retinas were evaluated from 1 to 9 months of age using immunohistochemistry, electroretinography, and fluorescein angiography. Retinal gene expression and statistically significant probe sets were categorized using analysis software. Select gene expression changes were confirmed with quantitative RT-PCR. RESULTS: In contrast to retinas from Nrl(-/-), those from Nrl(-/-)Grk1(-/-) exhibit a progressive loss of the outer nuclear layer, retinal physiology deficits, and a higher rate of degeneration with increasing age that is independent of environmental light exposure. Changes in retinal neovascularization occur in the Nrl(-/-)Grk1(-/-) at 1 month, before the onset of significant cone functional deficits. Microarray analyses demonstrate statistically significant changes in transcript levels of more than 400 genes, of which the oncostatin M signaling pathway and the inflammatory disease response network were identified. CONCLUSIONS: These data demonstrate that the loss of functional Grk1 on the enhanced S-cone Nrl(-/-) background exacerbates age-related cone dystrophy in a light-independent manner, mediated partly through the inflammatory response pathway and neovascularization. According to these findings, Grk1 helps to maintain a healthy cone environment, and the Nrl(-/-)Grk1(-/-) mouse allows examination of the alternative roles of Grk1 in cone photoreceptor homeostasis. |
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Authors:
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Rosanne M Yetemian; Bruce M Brown; Cheryl M Craft |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-04 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 51 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-02 Completed Date: 2011-01-13 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 6196-206 Citation Subset: IM |
Affiliation:
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Doheny Eye Institute, Department of Ophthalmology, Division of Retinal Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-9224, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology Animals Apoptosis Basic-Leucine Zipper Transcription Factors / physiology* Cell Survival Dark Adaptation Electroretinography Eye Proteins / physiology* Fluorescein Angiography G-Protein-Coupled Receptor Kinase 1 / physiology* Gene Silencing / physiology Immunohistochemistry In Situ Nick-End Labeling Light Mice Mice, Inbred C57BL Mice, Knockout Microarray Analysis Retinal Cone Photoreceptor Cells / pathology*, radiation effects Retinal Dystrophies / physiopathology* Retinal Neovascularization / physiopathology* Retinitis / physiopathology* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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EY015851/EY/NEI NIH HHS; EY03040/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic-Leucine Zipper Transcription Factors; 0/Eye Proteins; 0/Nrl protein, mouse; EC 2.7.1.37/Grk1 protein, mouse; EC 2.7.11.14/G-Protein-Coupled Receptor Kinase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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