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AIM: To explore the differentially expressed genes and crucial genes between epithelioid and mixed uveal melanoma(UM)based on bioinformatics analysis.METHODS: Microarray datasets GSE22138 was extracted from gene expression omnibus database(GEO). The differentially expressed genes(DEGs)were screened out between epithelioid and mixed UM, and functional enrichment analysis were performed with DAVID database. STRING and cytoscape was applied to explore the protein-protein interaction(PPI)network and hub genes. Subsequently, cBioPortal was applied to explore the network of the hub genes, and GEPIA was adopted to study the survival analysis of hub genes.RESULTS: Overall, 241 DEGs including 125 upregulated and 116 down regulated genes were identified. The DEGs mainly enriched in cell adhesion, response to drug and Positive regulation of endothelial cell proliferation. A total of 10 hub genes were identified. Survival analysis revealed the hub genes was associated with the prognosis of UM.CONCLUSION: DEGs and hub genes identified by Bioinformatics analysis in the present study would be beneficial to understand mechanism and biological characteristics between epithelioid and mixed UM.

The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover, post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.