Identification of apolipoprotein A-I as a "STOP" signal for myopia.
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.
Bertrand
Eric
E
Genome and Proteome Sciences, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
Fritsch
Christine
C
Diether
Sigrid
S
Lambrou
George
G
Müller
Dieter
D
Schaeffel
Frank
F
Schindler
Patrick
P
Schmid
Katrina L
KL
van Oostrum
Jan
J
Voshol
Hans
H
D000818:Animals; D016632:Apolipoprotein A-I / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D002645:Chickens; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000032:analysis / Q000378:metabolism*; D009216:Myopia / Q000209:etiology* / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists; D010671:Phenylurea Compounds / Q000494:pharmacology; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D012160:Retina / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development*; D012590:Sclera / Q000737:chemistry / Q000378:metabolism; D014746:Vimentin / Q000032:analysis / Q000378:metabolism
D016632:Apolipoprotein A-I; D002087:Butyrates; D005136:Eye Proteins; C453899:GW 7647; D047493:PPAR alpha; D010671:Phenylurea Compounds; D020543:Proteome; D014746:Vimentin