Stein Eye Institute, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA, 90095, USA.
Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Sci Rep. 2022 May 24;12(1):8705. doi: 10.1038/s41598-022-12770-9.
This study examines retinas from a rat glaucoma model for oxidized nucleosides 8OHdG and 8OHG, biomarkers for oxidative damage of DNA and RNA, respectively. Immunohistochemical data indicate a predominant localization of 8OHdG/8OHG in retinal ganglion cells (RGCs). The levels for these oxidized DNA/RNA products were 3.2 and 2.8 fold higher at 1 and 2 weeks after intraocular pressure elevation compared to control retinas, respectively. 8OHdG/8OHG were almost exclusively associated with mitochondrial DNA/RNA: ~ 65% of 8OHdG/8OHG were associated with RNA isolated from mitochondrial fraction and ~ 35% with DNA. Furthermore, we analyzed retinas of the rd10 mouse, a model for retinitis pigmentosa, with severe degeneration of photoreceptors to determine whether high levels of 8OHdG/8OHG staining intensity in RGCs of control animals is related to the high level of mitochondrial oxidative phosphorylation necessary to support light-evoked RGC activity. No significant difference in 8OHdG/8OHG staining intensity between control and rd10 mouse retinas was observed. The results of this study suggest that high levels of 8OHdG/8OHG in RGCs of wild-type animals may lead to cell damage and progressive loss of RGCs observed during normal aging, whereas ocular hypertension-induced increase in the level of oxidatively damaged mitochondrial DNA/RNA could contribute to glaucomatous neurodegeneration.
本研究检测了大鼠青光眼模型的视网膜中氧化核苷 8OHdG 和 8OHG 的水平，这两种物质分别是 DNA 和 RNA 氧化损伤的生物标志物。免疫组织化学数据表明，8OHdG/8OHG 主要定位于视网膜神经节细胞（RGCs）中。与对照组视网膜相比，眼压升高后 1 周和 2 周时，这些氧化 DNA/RNA 产物的水平分别升高了 3.2 倍和 2.8 倍。8OHdG/8OHG 几乎完全与线粒体 DNA/RNA 相关：从线粒体部分分离出的 RNA 中有65%与 8OHdG/8OHG 相关，有35%与 DNA 相关。此外，我们分析了 rd10 小鼠（一种视网膜色素变性模型）的视网膜，以确定控制动物中 RGC 中 8OHdG/8OHG 染色强度高是否与支持光诱发 RGC 活性所需的高水平线粒体氧化磷酸化有关。与 rd10 小鼠视网膜相比，对照组中 8OHdG/8OHG 染色强度没有显著差异。本研究结果表明，野生型动物 RGC 中高水平的 8OHdG/8OHG 可能导致正常衰老过程中观察到的细胞损伤和 RGC 逐渐丧失，而眼压升高导致氧化损伤的线粒体 DNA/RNA 水平增加可能导致青光眼性神经退行性变。
