Early detection of such retinal diseases as glaucoma and age-related macular degeneration (AMD) is important to prevent blindness. There have been reports of changes in some components in the tears of glaucoma and AMD patients, suggesting tears' potential usefulness in screening for retinal diseases. We hypothesized that retinal damage might alter gene expression in the lacrimal gland. We caused retinal damage in mice by intravitreal injection of N-methyl-D-aspartate (NMDA) or excessive light exposure. Hematoxylin and eosin staining showed no histological changes in the lacrimal glands of animals whose retinas had been damaged. However, RNA sequencing of lacrimal glands on the 3rd day after the retinal damage showed that several hundreds of gene expressions have altered in both the NMDA and light group. Further gene set enrichment analysis indicated that both types of retinal damage activated the immune system in the lacrimal glands. This study shows the first demonstration that retinal damage can alter gene expression in the lacrimal glands, and it might lead to a novel non-invasive screening method for retinal diseases.