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Research

Identification of Apolipoprotein A-I as a "STOP" Signal for Myopia^*

Eric Bertrand^,, Christine Fritsch^,¶, Sigrid Diether^||, George Lambrou^¶, Dieter Müller, Frank Schaeffel^||, Patrick Schindler, Katrina L. Schmid^**, Jan van Oostrum^, and Hans Voshol

From Genome and Proteome Sciences and ^¶ Neuroscience/Ophthalmology, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland, ^|| Section of Neurobiology of the Eye, University of Tuebingen, 72076 Tübingen, Germany, and ^** School of Optometry and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane Qld 4001, Australia

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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