Ocular Axial Growth Control and Proteomics: Differential Protein Expression in an Experimental Animal Model

Abstract

Abstract: : Purpose: Ocular axial length is an essential parameter of eye function. It is tightly controlled by an active process called emmetropization which sets the focal plane of the eye onto the retina. The growth process seems to be controlled by the retina, which sends signals to other eye structures. According to a common working hypothesis, the signal has two components: a default ‘GROW’ inducing signal and a ‘STOP’ growth inhibitory signal. Disturbance of emmetropization leads to defocus and vision impairment as the focal plane drifts behind (hyperopia) or in front of (myopia) the retina. In an effort to analyze the molecular mechanisms of axial growth control, we undertook an extensive proteome analysis of the retina in a chick model using high–resolution 2D gel electrophoresis and mass spectrometry (MS). Methods: Chicks were subjected to three types of applications: goggles and negative lenses which induce an elongation of the ocular globe (myopia) and positive lenses which induce a shortening of the ocular globe (hyperopia). A 2D–gel–based differential expression analysis was performed using a range of narrow–range pH gradient strips for the first dimension. Results: On a total of 37 differentially expressed spots, 32 were successfully analyzed by MS methods. Many of the identified spots are variants of the same protein, so the 32 identified spots correspond to 18 different proteins. Half of those are structural proteins (e.g. vimentin, tubulins), reflecting the morphological changes that take place during elongation of the eye. In addition, we found 2 proteins that display a profile corresponding to a ‘STOP’ signal (i.e. increased expression in Lens Induced Hyperopia) and 5 that display a profile corresponding to a ‘GROW’ signal (i.e. increased expression in Lens Induced Myopia or Form Deprivation). For confirmation and validation, we have been focusing on proteins with the most specific expression profiles and have, so far, confirmed one with a ‘STOP’ profile and another with a ‘GROW ’ profile. Conclusions: Our results support the existence of ‘GROW’ and ‘STOP’ signals in the retina which mediate axial eye growth on protein level and are interesting entry points for further investigations.

Keywords: myopia • proteomics • retina