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青光眼患者线粒体 DNA 损伤与眼血流的关系。

Association between mitochondrial DNA damage and ocular blood flow in patients with glaucoma.

出版信息

Br J Ophthalmol. 2019 Aug;103(8):1060-1065. doi: 10.1136/bjophthalmol-2018-312356. Epub 2018 Sep 6.

Abstract

BACKGROUND/AIMS: We determined the relationship between tissue mean blur rate (MT) and mitochondrial dysfunction, represented by the mitochondrial/nuclear DNA (mtDNA/nDNA) ratio. We also investigated the usefulness of these biomarkers.

METHODS

We assessed ocular blood flow in 123 eyes of 123 patients with open-angle glaucoma (OAG) and 37 control eyes of 37 healthy subjects by measuring MT in the optic nerve head with laser speckle flowgraphy. We measured mtDNA and nDNA with PCR, calculated the mtDNA/nDNA ratio and compared this ratio with MT using Spearman's rank test. We used multiple regression analysis to further investigate the association between MT and glaucoma in the most severe group.

RESULTS

The control and the patients with glaucoma had significant differences in the mtDNA/nDNA ratio, circumpapillary retinal nerve fibre layer thickness and MT. There was no significant relationship between the mtDNA/nDNA ratio and MT in patients with OAG overall or the female patients with OAG, but there was a significant relationship between the mtDNA/nDNA ratio and MT, temporal-MT and superior-MT in male patients with severe OAG (r=-0.46, p=0.03; r=-0.51, p=0.02; r=-0.61, p<0.01, respectively). Furthermore, we found that the mtDNA/nDNA ratio was an independent contributor to temporal-MT and superior-MT in these patients (p<0.01 and p=0.03, respectively).

CONCLUSION

We found that there was a significant relationship between the mtDNA/nDNA ratio and MT in male patients with severe OAG, suggesting that the mtDNA/nDNA ratio may be a new biomarker in glaucoma and may help research on the vulnerability of these patients to mitochondrial dysfunction.

摘要

背景/目的:我们确定了组织平均模糊率(MT)与线粒体功能障碍之间的关系,线粒体/核 DNA(mtDNA/nDNA)比值代表线粒体功能障碍。我们还研究了这些生物标志物的有用性。

方法

我们通过激光散斑血流图测量视神经头的 MT,评估了 123 例开角型青光眼(OAG)患者的 123 只眼和 37 名健康受试者的 37 只眼的眼部血流。我们通过 PCR 测量 mtDNA 和 nDNA,计算 mtDNA/nDNA 比值,并使用 Spearman 秩检验比较该比值与 MT。我们使用多元回归分析进一步研究最严重组中 MT 与青光眼之间的关系。

结果

对照组和青光眼患者的 mtDNA/nDNA 比值、全周视网膜神经纤维层厚度和 MT 有显著差异。在整体 OAG 患者或 OAG 女性患者中,mtDNA/nDNA 比值与 MT 之间无显著关系,但在严重 OAG 男性患者中,mtDNA/nDNA 比值与 MT、颞侧-MT 和上方-MT 之间存在显著关系(r=-0.46,p=0.03;r=-0.51,p=0.02;r=-0.61,p<0.01)。此外,我们发现 mtDNA/nDNA 比值是这些患者颞侧-MT 和上方-MT 的独立贡献者(p<0.01 和 p=0.03)。

结论

我们发现严重 OAG 男性患者 mtDNA/nDNA 比值与 MT 之间存在显著关系,提示 mtDNA/nDNA 比值可能是青光眼的一个新生物标志物,并可能有助于研究这些患者对线粒体功能障碍的易感性。

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