The study examined spontaneously myopic guinea pigs (n=11) versus hyperopic controls (n=12) in 2-week-old pigmented individuals using refraction, optical coherence tomography, ffERG, H&E staining, TUNEL assay, and Rapid-DIA retinal and plasma proteomics. Spontaneously myopic eyes had significantly more negative refractive error (p<0.0001), increased axial length (p=0.004), increased thickness of the choriocapillary layer (p<0.0001), thinner retina (p=0.008), choroid (p=0.0006) and sclera (p=0.002), as well as mosaic fundus. ERG responses were similar between groups, but the TUNEL assay showed increased apoptosis in the outer nuclear layer of the retina. Retinal proteomics revealed upregulated activation of complement, ferroptosis pathway and decreased expression of nitric oxide signaling protein. The expression of VEGF pathway proteins was increased in plasma. These guinea pigs show high similarity to human high myopia in ocular parameters, backgrounds and molecular pathways, making them a suitable model.