Document Detail


Wild-type cone photoreceptors persist despite neighboring mutant cone degeneration.
MedLine Citation:
PMID:  20053919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In many retinal diseases, the malfunction that results in photoreceptor loss occurs only in either rods or cones, but degeneration can progress from the affected cell type to its healthy neighbors. Specifically, in human and mouse models of Retinitis Pigmentosa the loss of rods results in the death of neighboring healthy cones. Significantly less is known about cone-initiated degenerations and their affect on neighboring cells. Sometimes rods remain normal after cone death, whereas other patients experience a loss of scotopic vision over time. The affect of cone death on neighboring cones is unknown. The zebrafish is a cone-rich animal model in which the potential for dying cones to kill neighboring healthy cones can be evaluated. We previously reported that the zebrafish cone phosphodiesterase mutant (pde6c(w59)) displays a rapid death of cones soon after their formation and a subsequent loss of rods in the central retina. In this study we examine morphological changes associated with cone death in vivo in pde6c(w59) fish. We then use blastulae transplantations to create chimeric fish with a photoreceptor layer of mixed wild-type (WT) and pde6c(w59) cones. We find that the death of inoperative cones does not cause neighboring WT cone loss. The survival of WT cones is independent of transplant size and location within the retina. Furthermore, transplanted WT cones persist at least several weeks after the initial death of dysfunctional mutant cones. Our results suggest a potential for the therapeutic transplantation of healthy cones into an environment of damaged cones.
Authors:
Alaron Lewis; Philip Williams; Owen Lawrence; Rachel O L Wong; Susan E Brockerhoff
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  30     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-07     Completed Date:  2010-02-04     Revised Date:  2011-05-17    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  382-9     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bystander Effect / physiology
Cell Death
Mutation / physiology*
Retinal Cone Photoreceptor Cells / cytology*,  physiology*
Retinal Degeneration / genetics*,  pathology*,  physiopathology
Zebrafish
Zebrafish Proteins / physiology
Grant Support
ID/Acronym/Agency:
5F32EY019210/EY/NEI NIH HHS; EY14358/EY/NEI NIH HHS; P30EY01733/EY/NEI NIH HHS; R01 EY018814-01A2/EY/NEI NIH HHS; R01EY018814/EY/NEI NIH HHS; T32EY007031/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Zebrafish Proteins
Comments/Corrections

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