TFE3 peptide

Gene- and cell-based therapies are promising strategies for the treatment of degenerative retinal diseases such as age-related macular degeneration, Stargardt disease, and retinitis pigmentosa. Cellular engineering before transplantation may allow the delivery of cellular factors that can promote functional improvements, such as increased engraftment or survival of transplanted cells. A current challenge in traditional DNA-based vector transfection is to find a delivery system that is both safe and efficient, but using mRNA as an alternative to DNA can circumvent these major roadblocks. In this study, we show that both unmodified and modified mRNA can be delivered to retinal pigmented epithelial (RPE) cells with a high efficiency compared with conventional plasmid delivery systems. On the other hand, administration of unmodified mRNA induced a strong innate immune response that was almost absent when using modified mRNA. Importantly, transfection of mRNA encoding a key regulator of RPE gene expression, microphthalmia-associated transcription factor (MITE), confirmed the functionality of the delivered mRNA. Immunostaining showed that transfection with either type of mRNA led to the expression of roughly equal levels of MITE, primarily localized in the nucleus. Despite these findings, quantitative RT-PCR analyses showed that the activation of the expression of MITE target genes was higher following toransfection with modified mRNA compared with unmodified mRNA. Our findings, therefore, show that modified mRNA transfection can be applied to human embryonic stem cell-derived RPE cells and that the method is safe, efficient, and functional.

Objectives: In order to provide further evidence for the origin and differentiation of PEComa, the clinicopathologic and immunophenotype findings were analyzed in 26 cases with literature review. Methods: Immunohistochemistry and special staining were used. Results: Multinucleated giant cells and polymorphism were scattered visibly in 53.8% and 76.9% of the cases and spotty necrosis and hemorrhage were observed in 38% of the cases. Capsular micro-invasion was detected in 46% cases accompanied by hemorrhage and/or necrosis in the tumors with diameters larger than 5 cm. It was also found that 100% of cases diffusely expressed SMA, Melan-A, and vimentin except one negative for HMB-45. The tumor cells partly expressed CD56, CD99, desmin, and S-100 and were negative for CK-pan, TFE3, CD117, CD44, and CD34. Clinical follow-up found that 22 out of 23 patients were alive, with no recurrence or progression, ranging from 42 to 82 months. However, one patient died from leukemia. Conclusions: In this study, the histopathologic features with the co-expressions of SMA and melanin, were the diagnostic basis of PEComas. The interspersed expressions of desmin and S-100 were helpful for the differential diagnosis of leiomyoma and neuroma. The expressions of S-100, CD56, and CD99 supported the origins of the pluripotent cells from the neural crests. Tumors larger than 5 cm in diameter with micro-hemorrhaging/necrosis and micro-capsular invasions should be considered either uncertain or of malignant potential. The spontaneous rupturing of blood vessels may be related to the amyloidosis and desmin negative expression, and broken elastic fibers.