Abstract: Objective: To explore the molecular mechanism and potential therapeutic targets of retinal ganglion cells(RGCs) apoptosis after optic nerve crush in mice. Methods: An optic nerve crush(ONC) mouse model was constructed, the retinal tissue was stained with HE staining to observe the histamathological changes, and the mRNA expression level of RGCs marker, RNA binding proteins with multiple splicing(Rbpms) was detected by reverse transcription-quantitative PCR(RT-qPCR). The mitochondrial damage of RGCs was observed by transmission electron microscopy(TEM). Transcriptomic sequencing was used to analyze the retinal differentially expressed genes of ONC 7 d group mice, and the differentially expressed genes were analyzed by Gene Ontology(GO) function, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment and Wayne analysis.The mRNA expression levels of differentially expressed genes were detected by RT-qPCR. Results: Compared with the normal group, the number of RGCs in the ONC 7 d group was significantly reduced, the cell arrangement was loose and irregular, and the mRNA expression level of RGCs marker Rbpms was significantly decreased(P<0.001). The ONC mouse model was successfully constructed. The results of TEM showed that the mitochondria of RGCs in the ONC 7 d group were swollen and the ridge disappeared. Transcriptome sequencing results showed that there were 562 differentially expressed genes in the ONC 7 d group compared with the normal group, among which 152 genes were down-regulated and 410 genes were up-regulated. GO functional enrichment analysis and KEGG pathway enrichment analysis showed that the differentially expressed genes after ONC were mainly concentrated in several important signaling pathways involved in neuronal damage repair. The RTqPCR results showed that compared with the normal group, the expression of Ecel1, Atf3, and Sprr1a genes related to neuronal damage repair was significantly up-regulated on the 4th day after injury(all P<0.05), which was consistent with the sequencing results. Conclusion: The apoptosis of RGCs in ONC mice is related to mitochondrial injury, and the Atf3, Ecel1 and Sprr1a genes related to neuronal damage repair are involved in the the early protection of RGCs after ONC in mice.