RNA VÒNG 0087207 THÚC ĐẨY QUÁ TRÌNH APOPTOSIS TRÊN TẾ BÀO HẠCH THẦN KINH VÕNG MẠC BIỆT HÓA TỪ TẾ BÀO GỐC VẠN NĂNG CỦA BỆNH NHÂN LEBER

Abstract

Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis level caused by mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. LHON mutation carrier phenotype suggests that disease’s pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction. The feature of incomplete penetrance indicates the importance of nuclear inheritance for the LHON phenotype. We compared the NGS data of iPSC-derived RGCs, including a family of normal, ND4 mutation carriers, and ND4 mutation-patients. We found that circRNA_0087207 had the most significantly higher expression level in the patient optic ganglion cells. In addition, overexpression of circRNA_0087207 in RGCs derived from ND4 mutation carriers can increase the level of apoptosis. In particular, overexpression of circRNA_0087207 in normal RGCs does not increase the apoptosis level. Inhibiting the expression of circRNA_0087207 in the patient cells can effectively reduce cell apoptosis. ND4 mutation is a necessary primary factor for optic neuropathy. Our results show that the circRNA_0087207 upregulation cooperated with ND4 mutation to regulate apoptosis in LHON-hiPSC derived RGCs.