Document Detail

The role of mislocalized phototransduction in photoreceptor cell death of retinitis pigmentosa.
MedLine Citation:
PMID:  22485131     Owner:  NLM     Status:  MEDLINE    
Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy.
Takeshi Nakao; Motokazu Tsujikawa; Shoji Notomi; Yasuhiro Ikeda; Kohji Nishida
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-02
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-09     Completed Date:  2012-07-27     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e32472     Citation Subset:  IM    
Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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MeSH Terms
Adenylate Cyclase / antagonists & inhibitors,  metabolism
Amino Acid Substitution
Animals, Genetically Modified
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors,  metabolism
Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics,  metabolism
Enzyme Inhibitors / pharmacology
Fish Proteins / genetics,  metabolism
Gene Knockdown Techniques
Mice, Inbred Strains
Protein Transport
Recombinant Proteins / genetics,  metabolism
Retinal Rod Photoreceptor Cells / enzymology,  physiology*,  radiation effects
Retinitis Pigmentosa / metabolism,  pathology*
Rhodopsin / genetics,  metabolism
Second Messenger Systems
Transducin / genetics,  metabolism
Vision, Ocular*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fish Proteins; 0/Recombinant Proteins; 60-92-4/Cyclic AMP; 9009-81-8/Rhodopsin; EC AMP-Dependent Protein Kinases; EC Nucleotide Phosphodiesterases, Type 6; EC 3.6.1.-/Transducin; EC Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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