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在渗出性年龄相关性黄斑变性患者中,自噬蛋白 Beclin-1 和 mTOR 的血清水平发生改变。

Altered serum levels of autophagy proteins Beclin-1 and mTOR in patients with exudative age-related macular degeneration.

机构信息

Jagiellonian University Medical College, Faculty of Medicine, Chair of Ophthalmology, Cracow, Poland.

Jagiellonian University Medical College, Faculty of Medicine, Division of Molecular Biology and Clinical Genetics, Cracow, Poland.

出版信息

J Physiol Pharmacol. 2021 Feb;72(1). doi: 10.26402/jpp.2021.1.09. Epub 2021 Feb 21.

Abstract

Autophagy is a key process in the maintenance of cellular survival and homeostasis. Inhibition of autophagy results in degenerative changes resembling ageing. We wondered if autophagy can contribute to the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate the serum concentrations of two key autophagy regulators, Beclin-1 and mechanistic target of rapamycin (mTOR), in patients with exudative AMD. This retrospective case-control study included 38 patients with exudative AMD and 36 sex- and age-matched controls selected among senile cataract patients. Circulating Beclin-1 and mTOR were assessed using an enzyme-linked immunosorbent assay. The proteins levels were correlated with age, sex, duration of ocular symptoms, as well as angiographic and optical coherence tomography findings. Serum Beclin-1 levels were much lower in patients with AMD than in controls (median, 0.100 ng/ml versus 1.123 ng/ml; p = 0.0033), while mTOR levels did not differ (median, 4.377 ng/ml versus 3.608 ng/ml; p = 0.4522). Participants of the study older than 70 years had lower Beclin-1 levels than younger ones (p = 0.0444). However, this difference was the most evident in patients with AMD (p = 0.0024). Serum mTOR levels increased with age. In patients with AMD, lower mTOR levels were associated with drusen, while higher levels were observed in those with a fibrous scar in the contralateral eye (p = 0.0212). Our findings suggest that circulating Beclin-1 decreases with age and that is downregulated in patients with AMD.

摘要

自噬是维持细胞存活和体内平衡的关键过程。自噬的抑制会导致类似于衰老的退行性变化。我们想知道自噬是否有助于年龄相关性黄斑变性(AMD)的发病机制。我们旨在研究渗出性 AMD 患者血清中两种关键自噬调节剂 Beclin-1 和雷帕霉素靶蛋白(mTOR)的浓度。这项回顾性病例对照研究纳入了 38 名渗出性 AMD 患者和 36 名性别和年龄匹配的老年性白内障患者作为对照组。采用酶联免疫吸附试验检测循环 Beclin-1 和 mTOR。蛋白水平与年龄、性别、眼部症状持续时间以及血管造影和光学相干断层扫描结果相关。AMD 患者的血清 Beclin-1 水平明显低于对照组(中位数 0.100ng/ml 比 1.123ng/ml;p = 0.0033),而 mTOR 水平无差异(中位数 4.377ng/ml 比 3.608ng/ml;p = 0.4522)。年龄大于 70 岁的参与者 Beclin-1 水平低于年龄较小者(p = 0.0444)。然而,这种差异在 AMD 患者中最为明显(p = 0.0024)。血清 mTOR 水平随年龄增加而升高。在 AMD 患者中,较低的 mTOR 水平与玻璃膜疣有关,而在对侧眼有纤维瘢痕的患者中观察到较高的 mTOR 水平(p = 0.0212)。我们的研究结果表明,循环 Beclin-1 随年龄而减少,并且在 AMD 患者中下调。

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