Effects of the tyrosinase-dependent dopaminergic system on refractive error development in Guinea pigs

Abstract

PURPOSE. To determine if myopia in albino guinea pigs is linked to altered ocular dopamine (DA) levels in both the retinal and uveal dopaminergic systems. METHODS. Retina and retinal pigment epithelium (RPE)/choroid were dissected from eyes of 2-week-old albino myopic (AM) and pigmented hyperopic (PH) guinea pigs. The levels of DA, dihydroxy-phenyl acetic acid (DOPAC), and homovanillic acid (HVA) were determined. Tyrosine hydroxylase (TH) and tyrosinase activities were also measured. PH animals received daily unilateral peribulbar injections of either kojic acid (tyrosinase inhibitor) or vehicle for 2 to 4 weeks. Refractive errors and ocular axial dimensions were measured by eccentric infrared photoretinoscopy and A-scan ultrasonography. RESULTS. Retinal DA levels were similar between the two strains, but AM eyes had higher levels of DOPAC. RPE/choroid DA and tyrosinase activity in AM eyes were lower than in PH eyes (P < 0.01); however, the DA turnover was higher (P < 0.05). After 2 weeks of kojic acid treatment, PH eyes developed significant myopia, accompanied by elongated vitreous chambers and axial lengths. Inhibition of tyrosinase activity was linearly correlated with a myopic refraction shift (R ¼ 0.79, P < 0.01). PH animals that received 62.5 ng/mL kojic acid treatment daily for 2 weeks followed by 625 ng/mL for 2 more weeks became more myopic and had deeper anterior chambers compared to those that received the 62.5 ng/mL dose over this period (P ¼ 0.04). CONCLUSIONS. The uveal tyrosinase-dependent dopaminergic system is involved in the development of guinea pig refraction. Enhancing uveal tyrosinase activity might slow down the development of myopia.