Article

Identification of apolipoprotein A-I as a "STOP" signal for myopia.

Genome and Proteome Sciences, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
Molecular &amp Cellular Proteomics (impact factor: 7.4). 12/2006; 5(11):2158-66. DOI:10.1074/mcp.M600073-MCP200
Source: PubMed

ABSTRACT Good visual acuity requires that the axial length of the ocular globe is matched to the refractive power of the cornea and lens to focus the images of distant objects onto the retina. During the growth of the juvenile eye, this is achieved through the emmetropization process that adjusts the ocular axial length to compensate for the refractive changes that occur in the anterior segment. A failure of the emmetropization process can result in either excessive or insufficient axial growth, leading to myopia or hyperopia, respectively. Emmetropization is mainly regulated by the retina, which generates two opposite signals: "GO/GROW" signals to increase axial growth and "STOP" signals to block it. The presence of GO/GROW and STOP signals was investigated by a proteomics analysis of the retinas from chicken with experimental myopia and hyperopia. Of 18 differentially expressed proteins that were identified, five displayed an expression profile corresponding to GO/GROW signals, and two corresponded to STOP signals. Western blotting confirmed that apolipoprotein A-I (apoA-I) has the characteristics of a STOP signal both in the retina as well as in the fibrous sclera. In accordance with this, intraocular application of the peroxisome proliferator-activated receptor alpha agonist GW7647 resulted in up-regulation of apoA-I levels and in a significant reduction of experimental myopia. In conclusion, using a comprehensive functional proteomics analysis of chicken ocular growth models we identified targets for ocular growth control. The correlation of elevated apoA-I levels with reduced ocular axial growth points toward a functional relationship with the observed morphological changes of the eye.

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Keywords

axial length
 
comprehensive functional proteomics analysis
 
emmetropization process
 
experimental myopia
 
expression profile corresponding
 
fibrous sclera
 
functional relationship
 
GO/GROW signals
 
Good visual acuity
 
increase axial growth
 
insufficient axial growth
 
juvenile eye
 
observed morphological changes
 
ocular axial growth points
 
ocular axial length
 
ocular growth control
 
peroxisome proliferator-activated receptor alpha agonist GW7647
 
proteomics analysis
 
refractive changes
 
STOP signals