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Molecular Mechanism of High Glucose Induced Mitochondrial DNA Damage in Retinal Ganglion Cells

Jinzi Zhou, Fenghua Chen, Aimin Yan, Xiaobo Xia

Background: Progressive death of retinal ganglion cells (RGCs) is the main pathological basis of glaucoma. It is found that mitochondrial DNA damage in RGCs may be closely related to lesion of glaucoma.

Methods: RGCs were cultured with different concentration of glucose and divided into 3 groups, namely NC group, Low-Glu group, High-Glu group. Cell counting kit-8 was used to detect the cell viability. Flow cytometry was used to detect the cell apoptosis. The DNA damage was measured with comet assay, and the morphological changes of damaged mitochondria in RGCs were observed by transmission electron microscopy (TEM). Western blot analyzed the expression of MRE11, RAD50, and NBS1 protein.

Results: Cell viability of RGCs in Low-Glu and High-Glu groups were lower than that in NC group in 48 and 96 h, *P<0.05, **P<0.01. The cell apoptosis in NC group was 4.9%, the Low-Glu group was 12.2% and High-Glu group was 24.4%. The comet imaging showed that NC cells did not have tailings, but the low-Glu and high-Glu group cells had tailings, indicating that the DNA of RGCs had been damaged. TEM showed that RGCs cultured with high glucose occurred mitochondrial morphology changes and dysfunction. Expression of MRE11, RAD50, NBS1 proteins associated with DNA damage repair pathway in High-Glu group were declined compared with Low-Glu group, #P<0.05.

Conclusion: High glucose induces mitochondrial DNA damage and results in apoptosis of retinal ganglion cells in glaucoma.