Role of Glutamate Receptor-Related Genes in Myopia Occurrence and Visual Development

Purpose: Abnormal expression of glutamate receptors is believed to be associated with myopia. However, it is currently unclear which genes contribute to the occurrence of such diseases. This study aims to investigate the effects of glutamate receptor-related genes family on ocular growth and development in zebrafish. Methods: Morpholino oligonucleotide injection, CRISPR/Cas9 genome editing, quantitative reverse transcription polymerase chain reaction, eye parameter measurements, visual motor responses, optokinetic responses, immunofluorescent staining, TUNEL assays, and Haematoxylin-Eosin staining were utilized to evaluate the alterations in the eyes following the deletion of grik1, gria4a, gria4b, grm5a, and grm5b. Results: It was observed that, after silencing gria4a, gria4b, and grm5a, the eyes were smaller, but the axial length to equatorial axis ratio increased significantly, indicating impaired eye growth and a tendency toward myopia. Furthermore, a reduction in choroidal vascular endothelial fluorescence and a decrease in eye movement frequency were consistent with the previously mentioned results. Additionally, the deletion of grik1, gria4a, gria4b, grm5a, and grm5b led to reduced fluorescence in bipolar cells, amacrine cells, and RPE cells, as well as diminished ON and OFF responses in the visual motor responses. Conclusions: Glutamate receptor-related genes, especially gria4a, gria4b, and grm5a, are likely involved in the onset of myopia and the regulation of visual development. The role of glutamate receptors in the onset and progression of myopia warrants further investigation.