This work shows that (±)-RPE65-61 inhibition protected photoreceptor cells from the activation of cGAS-STING signal pathway, possibly through the inhibition of visual cycle and, consequently, through decrease of DNA light damage, in an acute mouse model of AMD, accompanied by suppressing the upregulation of the genes involved in apoptosis and inflammatory responses. This evidence concerns the gene RPE65 and age-related macular degeneration.