Backgrounds: Leber’s hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON.
Background: Transforaminal percutaneous endoscopic lumbar discectomy (TPELD) recently confirms its superiority compared to typical open discectomy in the treatment of very high-grade migrated disk herniation. In Vietnam, this technique has been applied in recent years; however; lack of reports and evidence. Objectives: In this study, the authors would like to share their surgical experience and report the initial results in their center, after successfully performing TPELD for very high-grade migrated disk herniation in 40 patients. Patients and methods: Forty patients, who underwent TPELD to remove the nucleus of very high-grade migrated disk herniation, were enrolled in this study. The study was carried out from April 2019 to April 2021. Preoperative and postoperative MRI were compared to demonstrate the removed disk. Postoperative visual analog score, oswestry disability index, and modified Macnab criteria were obtained after 1 month, 6 months, and 1 year and were compared. Results: There were no major complications related directly to this technique. Seven patients were operated at L3-4, 28 patients at L4-5, and 5 patients at l5-S1. Mean visual analog score for leg pain improved from 7.36±0.64 preoperatively to 1.22±1.16 at 6 months postoperatively and 1.34±1.47 at 1 year postoperatively (P<0.01). The mean preoperative oswestry disability index improved from 67.1±8.79 preoperatively to 12.1±13.48 at 1 year postoperatively (P<0.01). Excellent or good global outcomes were obtained in 95%. Conclusions: TPELD is a minimally invasive treatment with effective and safe results of very high-grade migrated disk herniation. Improvement of several pain scores can be observed in the 12-month follow-up after surgery.
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