Abstract
Objective: The underlying mechanism of refractive development-whether it is confined to the local eyeball or involves the central visual pathways-remains controversial. This study aimed to explore the effect of optic nerve crush (ONC) on refractive development and lens-induced myopia (LIM) in mice and its potential mechanism. Design: Laboratory experimental study. Subjects: Three-week-old C57BL/6 mice were used in this study. The animals were divided into the following experimental groups: ONC group versus sham surgery (SHAM) group; ONC combined with LIM (ONC-LIM) group versus SHAM combined with LIM (SHAM-LIM) group; LIM followed by ONC group verus LIM group versus plano lens group. Methods: The refraction and ocular biological parameters were measured. Bulk RNA-sequencing analysis was performed on retinas from the ONC group and the SHAM group. Differential expression analysis between groups was conducted using edgeR. Differentially expressed genes were selected by trend analysis to investigate the expression trends over different refractive conditions after ONC. The Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction analysis, and gene set enrichment analysis were conducted, and quantitative reverse transcription polymerase chain reaction was applied for validation. Main outcome measures: The axial length (AL). Results: The results indicated that, after ONC, 50% of the mice showed a myopic shift and 25% showed a hyperopic shift, and the changes in AL were consistent with refraction. The ONC-LIM group failed to develop myopic shift or axial elongation, unlike the SHAM-LIM group, suggesting that optical defocus could not induce a myopic shift in mice after ONC. RNA-sequencing analysis revealed several pathways associated with post-ONC refractive status, including glutamatergic synapse, gonadotropin-releasing hormone signaling, and long-term depression. Conclusions: Our findings suggest that intact optic nerve is necessary for normal murine emmetropization and for the development of LIM. While local ocular mechanisms remain the established paradigm for refractive regulation, our experimental results indicate the potential involvement of CNS pathways in ocular growth regulation. Further studies are needed to elucidate the precise mechanisms and potential interplay between local and central regulatory systems. Financial disclosures: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.