Myopia development and susceptibility vary across pigmentation backgrounds and ocular tissues, yet the underlying molecular mechanisms remain unclear. In this study, retina, choroid, and sclera were collected from albino and pigmented guinea pigs subjected to spontaneously developed hyperopia and myopia paradigms. Tissue proteins were labeled using 16-plex Tandem Mass Tags (TMT) and analyzed by Orbitrap LC-MS/MS to obtain tissue-resolved quantitative proteomes. Comparative analyses between Albino Hyperopia (AH), Pigmented Hyperopia (PH), and Albino Myopia (AM) groups aimed to identify protein networks and pathways associated with pigmentation heritage, extracellular matrix remodeling, and retinal signaling in myopia pathogenesis. The dataset provides peptide and protein-level quantification for three ocular tissues across all experimental conditions, enabling exploration of molecular mechanisms linking pigmentation and biomechanical regulation to eye growth control.