Retinal proteomic analysis reveals ON/OFF visual stimulation-specific changes in a Guinea pig myopia model

This study aimed to explore the effect of artificial dynamic ON/OFF stimulation on the development of myopia and associated retinal proteomic changes in guinea pigs, and elucidate the underlying mechanisms. Myopia was induced in one eye of guinea pigs using -4 diopters lenses, with the other eye used as the untreated control. 53 guinea pigs were randomly given balanced ON/OFF (natural control, NC), ON, or OFF stimulation for 7 days. The axial lengths and refractions were measured. The choroidal thickness was measured using HE-staining in 4 guinea pigs per group. The retinal proteome was analyzed by LC-MS/MS, and protein expression compared across groups. Myopic eyes exposed to ON and OFF stimulation exhibited a lower degree of myopia compared with NC myopic eyes. HE staining revealed that NC myopic eyes had a thinner choroid; there was no difference between the two eyes in the ON/OFF group. A total of 646 differentially expressed proteins (DEPs) were observed in the ON, OFF, and NC groups. ON/OFF-specific DEPs affected glycometabolism and RNA function. Reduced activity of the Rap1 signaling pathway was enriched in the both ON/NC DEPs. GZMK, NDFIP2, PARP12, ZC3HAV1, and ID1 were identified as common proteins that remained unaffected by visual stimulations but were implicated in myopia induction solely through negative lens exposure. The DEPs in the three groups also overlapped with proteins associated with human myopia. In conclusion, ON and OFF stimulation suppressed myopia in guinea pigs, with unique DEPs affected; the Rap1 signaling pathway may be a myopia intervention target; and DEPs common across groups are related to oxidative stress and inflammation. TRIAL REGISTRATION: wydw2023-0063/2023.3.5.