| Caspase-3 in postnatal retinal development and degeneration. | |
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MedLine Citation:
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PMID: 14985318 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The primary purpose of this study was to evaluate the impact of caspase-3 ablation on photoreceptor degeneration in the rd-1 mouse. Concurrently, the role of caspase-3 in postnatal retinal development was evaluated. Caspase-3 is an important effector caspase that mediates many of the terminal proteolytic events of apoptosis. Its activation has been demonstrated in rodent models of photoreceptor degeneration and its ablation results in exencephaly and neonatal death. METHODS: Retinal morphometry was performed at the light microscopic level in caspase-3 mutant mice from PN0 through PN23, and in rd-1/caspase-3 double mutant mice at PN14, -16, and -18. This was supplemented by terminal dUTP transferase nick end labeling (TUNEL) and immunohistochemical staining for activated caspase-3, rhodopsin, factor VII-related antigen and proliferating cell nuclear antigen (PCNA). RESULTS: Caspase-3-deficient animals display marginal microphthalmia, peripapillary retinal dysplasia, delayed regression of vitreal vasculature, and retarded apoptotic kinetics of the inner nuclear layer. Ablation of caspase-3 provided transient photoreceptor protection in rd-1, but TUNEL-positive rod death proceeded, despite the absence of caspase-3 activation. CONCLUSIONS: In vivo, caspase-3 is not critical for rod photoreceptor development, nor does it play a significant role in mediating pathologic rod death. Peripapillary dysplastic lesions suggest that there is delayed fusion of the optic fissure, and inner nuclear layer abnormalities indicate a cell-specific dependency on the mitochondria-caspase axis during development. The temporal nature of apoptotic retardation in the absence of caspase-3 implies the presence of caspase-independent mechanisms of developmental and pathologic cell death. |
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Authors:
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Caroline J Zeiss; Jason Neal; Elizabeth A Johnson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 45 ISSN: 0146-0404 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-02-26 Completed Date: 2004-03-18 Revised Date: 2008-11-21 |
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: 964-70 Citation Subset: IM |
Affiliation:
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Section of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA. caroline.zeiss@yale.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Antigens / metabolism Caspase 3 Caspases / physiology* Cell Death Enzyme Activation Factor VII / metabolism Female In Situ Nick-End Labeling Male Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Mutant Strains Photoreceptor Cells, Vertebrate / enzymology, pathology Proliferating Cell Nuclear Antigen / metabolism Retina / enzymology, growth & development* Retinal Degeneration / enzymology*, pathology Rhodopsin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens; 0/Proliferating Cell Nuclear Antigen; 0/factor VII related antigen; 9001-25-6/Factor VII; 9009-81-8/Rhodopsin; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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