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α-突触核蛋白在视网膜中的过度表达可导致视力损伤和多巴胺能无长突细胞变性。

α-synuclein overexpression in the retina leads to vision impairment and degeneration of dopaminergic amacrine cells.

机构信息

Telethon Institute of Genetics and Medicine, Telethon Foundation, Pozzuoli, Naples, Italy.

Institute for Genetic and Biomedical Research (IRGB), National Research Council (CNR), Milan, Italy.

出版信息

Sci Rep. 2020 Jun 15;10(1):9619. doi: 10.1038/s41598-020-66497-6.

Abstract

The presence of α-synuclein aggregates in the retina of Parkinson's disease patients has been associated with vision impairment. In this study we sought to determine the effects of α-synuclein overexpression on the survival and function of dopaminergic amacrine cells (DACs) in the retina. Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. Before and after systemic injections of levodopa (L-DOPA), retinal responses and visual acuity-driven behavior were measured by electroretinography (ERG) and a water maze task, respectively. Amacrine cells and ganglion cells were counted at different time points after the injection. α-synuclein overexpression led to an early loss of DACs associated with a decrease of light-adapted ERG responses and visual acuity that could be rescued by systemic injections of L-DOPA. The data show that α-synuclein overexpression affects dopamine neurons in the retina. The approach provides a novel accessible method to model the underlying mechanisms implicated in the pathogenesis of synucleinopathies and for testing novel treatments.

摘要

在帕金森病患者的视网膜中存在α-突触核蛋白聚集物与视力障碍有关。在这项研究中,我们试图确定α-突触核蛋白过表达对视网膜中多巴胺能无长突细胞(DAC)存活和功能的影响。成年小鼠通过玻璃体内注射腺相关病毒(AAV)载体在内视网膜中过表达人野生型α-突触核蛋白。在给予左旋多巴(L-DOPA)全身注射前后,通过视网膜电图(ERG)和水迷宫任务分别测量视网膜反应和视力驱动行为。在注射后不同时间点计数无长突细胞和节细胞。α-突触核蛋白过表达导致与光适应 ERG 反应和视力下降相关的 DAC 早期丢失,这些可通过 L-DOPA 的全身注射得到挽救。该数据表明α-突触核蛋白过表达影响视网膜中的多巴胺神经元。该方法为模拟与突触核蛋白病发病机制相关的潜在机制以及测试新疗法提供了一种新颖的可及方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7ee/7295803/7692e976312c/41598_2020_66497_Fig1_HTML.jpg

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