Rhodopsin Induces Myopia via Lipid Peroxidation in Zebrafish Reared in a Dark Environment

Outdoor time and light intensity are important emerging factors affecting myopia; however, the underlying mechanisms remain unknown. This study aimed to clarify whether a dark environment induces myopia in zebrafish and investigate the role of rhodopsin in this process. To this end, zebrafish were reared in a dark environment, and myopia-related parameters were measured. RNA sequencing and histological analysis were performed. We found a myopic shift with a relative refractive error (RRE) change and an increased eye-to-body length ratio in zebrafish reared in the dark compared to that in their light-reared siblings. RNA sequencing indicated that the phototransduction pathway was affected. Hematoxylin-eosin staining and immunofluorescence analysis confirmed the elongation of the rod's outer segment and increased rhodopsin expression. Overexpressed rhodopsin determined a myopic RRE; ocular enlargement resembled myopia and elevated 4-hydroxynonenal (4-HNE), which was also present in the retinal pigment epithelium of the dark-reared zebrafish. Incubation of ARPE-19 cells with a low 4-HNE concentration increased cell proliferation capacity, while incubation of ARPE-19 cells with its high concentration induced apoptosis. The increased expression of rhodopsin in a dark-rearing environment affected refractive development in zebrafish.