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

Bertrand, Eric, Fritsch, Christine, Diether, Sigrid, Lambrou, George, Mueller, Dieter, Schaeffel, Frank, Schindler, Patrick, Schmid, Katrina L., van Oostrum, Jan van, & Voshol, Hans (2006) Identification of apolipoprotein A-I as a "STOP" signal for myopia. Molecular & Cellular Proteomics, 5(11), pp. 2158-2166.

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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 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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15 citations in Web of Science®

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ID Code: 9891
Item Type: Journal Article
DOI: 10.1074/mcp.M600073-MCP200
ISSN: ISBN: 1535-9476
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > OPTOMETRY AND OPHTHALMOLOGY (111300) > Vision Science (111303)
Divisions: Current > Research Centres > Centre for Health Research
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 American Society for Biochemistry and Molecular Biology
Copyright Statement: Reproduced in accordance with the copyright policy of the publisher.
Deposited On: 10 Jan 2008
Last Modified: 29 Feb 2012 23:23

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