Document Detail


Regulation of posttranscriptional modification as a possible therapeutic approach for retinal neuroprotection.
MedLine Citation:
PMID:  21076532     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Understanding pathogenesis at the molecular level is the first step toward developing new therapeutic approaches. Here, we review the molecular mechanisms of visual dysfunction in two common diseases, innate chorioretinal inflammation and diabetic retinopathy, and the role of the ubiquitin-proteasome system (UPS) in both processes. In innate chorioretinal inflammation, interleukin-6 family ligands induce STAT3 activation in photoreceptors, which causes UPS-mediated excessive degradation of the visual substance, rhodopsin. In diabetic retinopathy, angiotensin II type 1 receptor (AT1R) signaling activates ERK in the inner layers of the retina, causing UPS-mediated excessive degradation of the synaptic vesicle protein, synaptophysin. This latter effect may decrease synaptic activity, in turn adversely affecting neuronal survival. Both mechanisms involve increased UPS activity and the subsequent excessive degradation of a protein required for visual function. Finally, we review the therapeutic potential of regulating the UPS to protect tissue function, citing examples from clinical applications in other medical fields.
Authors:
Yoko Ozawa; Toshihide Kurihara; Kazuo Tsubota; Hideyuki Okano
Publication Detail:
Type:  Journal Article     Date:  2010-11-07
Journal Detail:
Title:  Journal of ophthalmology     Volume:  2011     ISSN:  2090-0058     ISO Abbreviation:  J Ophthalmol     Publication Date:  2011  
Date Detail:
Created Date:  2010-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101524199     Medline TA:  J Ophthalmol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  506137     Citation Subset:  -    
Affiliation:
Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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