Kaarniranta Kai, Pawlowska Elzbieta, Szczepanska Joanna, Blasiak Janusz
1Department of Ophthalmology, University of Eastern Finland, Kuopio 70211, Finland and Department of Ophthalmology, Kuopio University Hospital, Kuopio 70029, Finland.
2Department of Orthodontics, Medical University of Lodz, 92-216 Lodz, Poland.
Aging Dis. 2020 Jul 23;11(4):851-862. doi: 10.14336/AD.2019.0809. eCollection 2020 Jul.
DICER1 deficiency in the retinal pigment epithelium (RPE) was associated with the accumulation of transcripts and implicated in geographic atrophy (GA), a form of age-related macular degeneration (AMD), an eye disease leading to blindness in millions of people. Although the exact mechanism of this association is not fully known, the activation of the NLRP3 inflammasome, maturation of caspase-1 and disruption in mitochondrial homeostasis in RPE cells were shown as critical for it. DICER1 deficiency results in dysregulation of miRNAs and changes in the expression of many genes important for RPE homeostasis, which may also contribute to AMD. DICER1 deficiency can change the functions of the miR-183/96/182 cluster that regulates photoreceptors and their synaptic transmission. Aging, the main AMD risk factor, is associated with decreased expression of DICER1 and changes in its diurnal pattern that are not synchronized with circadian regulation in the retina. The initial insult inducing DICER1 deficiency in AMD may be oxidative stress, another major risk factor of AMD, but further studies on the role of deficient DICER1 in AMD pathogenesis and its therapeutic potential are needed.
视网膜色素上皮（RPE）中的DICER1缺陷与转录本的积累有关，并与地图状萎缩（GA）有关，GA是年龄相关性黄斑变性（AMD）的一种形式，AMD是一种导致数百万人失明的眼病。尽管这种关联的确切机制尚不完全清楚，但已表明RPE细胞中NLRP3炎性小体的激活、caspase-1的成熟以及线粒体稳态的破坏对此至关重要。DICER1缺陷导致miRNA失调以及许多对RPE稳态重要的基因表达发生变化，这也可能导致AMD。DICER1缺陷会改变调节光感受器及其突触传递的miR-183/96/182簇的功能。衰老作为AMD的主要危险因素，与DICER1表达降低及其昼夜模式变化有关，且这种变化与视网膜中的昼夜节律调节不同步。在AMD中引发DICER1缺陷的初始损伤可能是氧化应激，氧化应激是AMD的另一个主要危险因素，但仍需要进一步研究DICER1缺陷在AMD发病机制中的作用及其治疗潜力。
