Dynamic ON stimulation preserves choroidal homeostasis and attenuates lens-induced myopia in guinea pigs

Purpose To characterize refractive changes, choroidal responses, and dopamine (DA) release patterns associated with susceptibility to artificial dynamic ON and OFF stimulation during the development of lens-induced myopia (LIM) in guinea pigs. Methods Sixty-three guinea pigs were randomly assigned to ON, OFF, and natural control (NC) stimulation for 12 h/day over 7 days. Lens-induced myopia was induced with a − 4 D monocular lens. Refraction, axial length (AL), choroidal thickness (ChT), and choroidal blood perfusion (ChBP) were assessed before and after treatment. DA and its metabolites in the vitreous and retina were quantified by high-performance liquid chromatography (HPLC), and choroidal proteomes were profiled by liquid chromatography–tandem mass spectrometry (LC–MS/MS) followed by bioinformatic analysis. Results ON stimulation resulted in significantly less myopia in LIM eyes than NC and OFF (ON: −2.075 ± 0.4992 D vs. NC: −4.183 ± 0.3474 D, p = 0.0038; OFF: −4.546 ± 0.3694 D, p = 0.0004). Across groups, greater myopic shift was accompanied by increased AL. LIM induced significant choroidal thinning in the NC and ON groups (NC: −7.969 ± 1.618 vs. +4.650 ± 1.824 µm in fellow control eyes, p < 0.0001; ON: −5.840 ± 1.928 vs. +2.096 ± 1.487 µm, p = 0.0194), whereas it was not significant in the OFF group. In non-lens eyes, ON stimulation produced higher ChBP than NC or OFF stimulation, and ChT changes were positively correlated with ChBP under all conditions (p < 0.0001). Under LIM, vitreal DA and homovanillic acid (HVA) levels were significantly lower in the NC and OFF groups than in the ON group, indicating relatively preserved dopaminergic signaling with ON. In non-lens eyes, retinal DA and 3,4-dihydroxyphenylacetic acid were lower under ON and OFF stimulation. Proteomic analysis revealed distinct choroidal remodeling signatures among ON, OFF, and NC groups, with ON stimulation associated with the smallest number of differentially expressed proteins and a relatively preserved pattern of collagen and fibrillin expression compared with more pronounced the Extracellular Matrix (ECM) depletion under NC and over-compensatory ECM upregulation under OFF stimulation. Conclusion In this guinea pig model of lens-induced myopia, dynamic ON stimulation was associated with less myopic progression compared with NC and OFF conditions, potentially by preserving retinal dopaminergic signaling and promoting a more homeostatic pattern of choroidal collagen/fibrillin remodeling.