Association Between Pigmentation Heritage and Susceptibility to Experimentally Induced Myopia: Crossbreeding Insights...

To investigate how pigmentation heritage affects susceptibility to form deprivation myopia (FDM) through crossbreeding myopia-susceptible albino and myopia-resistant pigmented guinea pigs (GPs).

Ninety GPs (albino: n = 29, pigmented: n = 29, F1 crossbred: n = 32) were studied. Eye parameters were measured using retinoscopy and A-scan ultrasound. Scotopic electroretinograms were recorded by full-field electroretinography in 36 naive GPs at 1 and 5 weeks of age. Monocular form deprivation (FD) was applied from 1 to 5 weeks of age in 27 GPs, with 27 littermates as controls. The retina, choroid, and sclera were imaged using optical coherence tomography. From control GPs at 5 weeks, scleral melanin was assessed histologically; choroidal melanin and tyrosinase activity in the choroid and sclera were quantified biochemically.

Crossbreds had a pigmented appearance, and choroidal thickness (ChT, 100 ± 19 µm) was thicker than in albino GPs (69 ± 12 µm, P < 0.001) but thinner than in pigmented GPs (124 ± 19 µm, P = 0.004). Choroidal melanin content and tyrosinase activity followed similar patterns and were significantly different (one-way ANOVA): highest in pigmented GPs, intermediate in crossbreds, and undetectable in albinos. Albinos exhibited the largest a-wave amplitudes across the intensity-response functions among the three breeds. Crossbreds displayed a monotonic b-wave intensity-response function, similar to but with higher amplitudes than pigmented GPs, whereas albinos showed a bell-shaped response pattern before the second rise. FD induced significant myopic shift and axial elongation in albinos (spherical equivalent [SE]: -7.83 ± 4.74 D, P = 0.001; axial length [AL]: 0.20 ± 0.14 mm, P = 0.003) and crossbreds (SE: -5.42 ± 2.90 D, P < 0.001; AL: 0.17 ± 0.09 mm, P = 0.001). Pigmented GPs showed a mild myopic shift (-2.08 ± 1.93 D, P = 0.01) with no significant AL changes (0.03 ± 0.08 mm, P = 0.357). FDM severity differed across breeds (SE: P = 0.006, AL: P = 0.004); thicker baseline ChT was associated with less FDM in crossbreds (P = 0.027) and reduced axial elongation in albinos (P = 0.004); retinal and scleral thicknesses were nonpredictive.

Crossbreeding improved retinal function and choroidal morphology, while preserving susceptibility to FDM, suggesting a partial restoration of myopia-inducible mechanisms inherited from the albino lineage. These findings support the value of the crossbred model for investigating retinal and choroidal regulation in myopia.