Quantitative proteomic analysis of scleras in guinea pig exposed to wavelength defocus

Myopia is the most common optical disorder in the world, and wavelength defocus induced ametropia and myopia have attracted great attention. The objective was to identify and quantify scleral proteins involved in the response to the wavelength defocus. Guinea pigs were randomly divided into 3 groups that received different lighting conditions for 8 weeks: white light, short wavelength light, and long wavelength light. Refraction and axial length were measured, Hematoxylin-Eosin staining and transmission electron microscope were adopted to observe the scleral structure, and scleral proteome was also detected to analyze protein abundance by employing TMT labeling method. After light stimulation, the long- and short -wavelength light induced myopic and hyperopic effect on the guinea pig's eye and induced distinct protein signature, respectively. 186 dyregulated proteins between the short- and long-wavelength group were identified, which were mainly located in extracellular region and involved in metabolic process. We also found that 5 proteins in the guinea pigs scleras in response to wavelength defocus were also human myopic candidate targets, suggesting functional overlap between dyregulated proteins in scleral upon exposure to wavelength defocus and genes causing myopia in humans. SIGNIFICANCE: Wavelength defocus induces refractive errors and leads to myopia or hyperopia. However, sclera proteomics respond to wavelength defocus is lacking, which is crucial to understanding how wavelength defocus influences refractive development and induces myopia. In this proteome analysis, we identified unique protein signatures response to wavelength defocus in sclera of guinea pigs, identified potential mechanisms contributing to myopia formation, and found that several human myopia-related genes may involve in response to wavelength defocus. The results of this study provide a foundation to understand the mechanisms of myopia and wavelength defocus induced ametropia.