Role of tyrosinase in ocular growth and myopia development in a guinea pig model

Tyrosinase participates in melanin synthesis and may also contribute to L-3,4-dihydroxyphenylalanine (L-DOPA)-related dopamine metabolism during development. Because dopamine (DA)-related signaling has been implicated in visually guided ocular growth, this study investigated whether tyrosinase-related pathways are associated with refractive development and susceptibility to lens-induced myopia (LIM) in guinea pigs. A total of 48 pigmented and 32 albino guinea pigs at 3 weeks of age were included. Animals were divided into five groups: pigmented guinea pigs with LIM and kojic acid treatment (PLK), pigmented guinea pigs with LIM only (PL), albino guinea pigs with LIM (AL), pigmented baseline controls (PH), and albino baseline controls (AM). LIM was induced using a - 10 D lens in the right eye, with the fellow eye serving as the contralateral control. In the PLK group, kojic acid, a tyrosinase inhibitor, was administered by peribulbar injection for 4 weeks. Refractive error, axial length (AL), ocular biometric parameters, retinal thickness, choroidal thickness (ChT), and choroidal blood perfusion (ChBP) were assessed. ELISA-measured tyrosinase levels and neurotransmitter profiles were also analyzed. At baseline, albino guinea pigs showed a relatively more myopic refractive status, longer AL, altered ocular biometric parameters, reduced ChT, and lower ChBP compared with pigmented guinea pigs. ELISA-measured tyrosinase levels were lower in albino guinea pigs than in pigmented guinea pigs across ocular tissues. Dopamine levels did not differ significantly between strains, whereas 3,4-dihydroxyphenylacetic acid (DOPAC) levels were reduced in albino guinea pigs, suggesting altered dopamine turnover. In pigmented guinea pigs, kojic acid treatment accelerated LIM-induced myopic progression and axial elongation. LIM-associated retinal thinning was mainly localized to the temporal retina. At the endpoint, ELISA-measured tyrosinase levels showed tissue-specific changes, with decreases in the vitreous and choroid and an increase in the retina of LIM-treated eyes. Albino guinea pigs showed a more myopic baseline phenotype, longer axial length, reduced choroidal thickness and perfusion, and lower ELISA-measured tyrosinase levels than pigmented guinea pigs. The reduction in DOPAC, despite unchanged absolute dopamine levels, suggests altered dopamine turnover. Kojic acid treatment further enhanced LIM-induced myopic progression and axial elongation in pigmented guinea pigs, indicating that tyrosinase-related pathways may influence susceptibility to myopia. As tyrosinase enzymatic activity was not directly measured, these findings should be interpreted cautiously as associations among ELISA-measured tyrosinase levels, dopamine metabolism, and retinal/choroidal changes.