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