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.