Cell Rep:表观基因组可作一种治疗策略来预防视力丧失

2020-04-24 竹子 转化医学网

导言:近日,国立卫生研究院的一部分,美国国立眼科研究所(NEI)的研究人员对光感小鼠感光细胞的表观基因组变化进行了分析,从而更加清晰地了解了与年龄相关的眼部疾病可能与年龄相关的基因表达调控的变化相关联

导言:近日,国立卫生研究院的一部分,美国国立眼科研究所(NEI)的研究人员对光感小鼠感光细胞的表观基因组变化进行了分析,从而更加清晰地了解了与年龄相关的眼部疾病可能与年龄相关的基因表达调控的变化相关联。该发现于4月21日在线发表在《细胞报告》(Cell Reports)上,表明表观基因组可以作为一种治疗策略来预防视力丧失,如年龄相关性黄斑变性(AMD)。

研究阐明了与杆状感光细胞、视网膜光敏细胞衰老有关的分子变化和生物学途径。未来的研究可以进一步研究如何预防或延缓衰老过程中的视力丧失,并有望降低相关神经退行性风险。
每个生物体都有一个基因组,一个控制人体所有细胞和组织功能的基因库。这些基因的表达(当存储在DNA中的信息转换成用于制造蛋白质或其他分子的指令时)由有机体的表观基因组进行调节和维持。表观基因组标记了DNA编码,以对生存有利和不利的方式修饰基因表达。

事实证明,基因组与表观基因组之间的相互作用随着生物体的衰老而发展。因此,科学家研究了表观基因组DNA修饰,以寻找某些疾病随着年龄的增长而发展的线索。

该研究的首席研究员,NEI神经生物学、神经变性和修复实验室的高级研究员兼负责人阿南德·斯沃普(Anand Swaroop)博士及其团队,为了探索随着年龄的增长这种DNA修饰会如何影响视觉功能,他们在小鼠的一生中分了四个不同的阶段,对小鼠杆状光感细胞中的DNA甲基化变化进行了全基因组测序。DNA甲基化是正常细胞发育和分化必不可少的表观遗传机制,并且还与衰老和癌症形成有关,出现时通常会抑制基因表达。

测序年龄分别为三个月(年轻),12个月(中年)以及18和24个月(年长)。小鼠的平均寿命约为两年。

杆状光感细胞是视网膜中主要的细胞类型,是眼后部的光敏组织。它能让人在昏暗情况下也有视觉,并且对于实现日光和彩色视觉的锥形感光细胞的生存至关重要。杆功能障碍在老年人中很常见,可能是AMD和其他视网膜变性疾病的预警信号。


这是一张显示了AMD患者视觉效果中杂货店过道外观的模拟图。AMD损害了黄斑,黄斑是眼睛感光视网膜中心附近的一个小斑点。黄斑使人能够看到笔直的物体,此部分用于集中视线。

研究人员在四个小鼠年龄组中鉴定了2,054个差异甲基化区域,即DNA甲基化差异的基因组区域。DNA甲基化的变化与生物学年龄密切相关,但是在进行这项研究之前,研究人员对这些变化与细胞功能之间的关系了解有限。

然后,研究人员利用RNA测序数据分析了甲基化区域的差异,从而更仔细地观察了小鼠基因如何随着动物的衰老而在视网膜中转录不同的蛋白质。

这些分析揭示了基因如何产生能量代谢,线粒体功能和杆状光感受器寿命有关的蛋白质的明显变化,表明它们对与年龄相关的疾病易感性的贡献。

杆状感光细胞需要大量能量来维持视力,因此容易受到衰老带来的新陈代谢压力的影响。感光细胞的能量缺乏是视网膜神经变性的关键驱动力。研究表明了衰老杆功能的变化如何使其容易受到遗传易感性变化和环境因素的影响,共同导致常见的致盲性衰老相关疾病。

研究提供了衰老、表观基因组、细胞线粒体功能障碍和诸如AMD等疾病之间的关键联系。这些发现对人们如何理解与年龄相关的神经退行性疾病具有广泛的意义。这是第一个研究DNA甲基化随动物年龄增长而变化的研究。未来的研究将评估DNA甲基化是否有助于代谢基因表达的改变,从而引入表观基因组编辑作为年龄相关性视网膜疾病的治疗可能性。

原始出处:

Corso-Díaz X, Gentry J, Rebernick R, et.al. Genomewide profiling identifies DNA methylation signatures of aging in rod photoreceptors associated with alterations in energy metabolism". Cell Reports Published April 21, 2020 in Cell Reports.

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    2020-10-12 docwu2019
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Ann R Coll Surg Engl:由筛鼻侵犯骨小梁的骨化纤维瘤造成单侧视力丧失的病例报告

英国诺里奇东英吉利大学的Ta NH等人近日在Ann R Coll Surg Engl杂志上发表了一篇病例报告,他们报告了一例鼻窦压迫右侧内侧的骨化纤维瘤,进而造成右侧视力损失的病例报告。

拓展阅读

指南共识:软组织填充剂引起的视力丧失治疗共识 2021

发生失明需要三个因素:注射压力超过收缩压,血管腔内有足够量的物质,物质逆行和随后顺行进入眼循环。

玻尿酸注射丰胸后,瞎了……

今天我们学习一个罕见的病例,在乳房注射 HA 填充剂后,继发于双侧 Purtscher 样视网膜病变和旁中央急性中黄斑病变 PAMM,继发全身并发症和视力丧失。

Neurology:见于Leber遗传性视神经病的黑质T2高信号

29岁酗酒男性,表现为突发右眼进行性中心视力丧失。

NICE推荐将诺华的Luxturna基因疗法用于治疗双等位RPE65突变引起的视力丧失

英国国家健康与护理卓越研究所(NICE)已建议在NHS上使用诺华的Luxturna(voretigene neparvovec)用于治疗RPE65介导的遗传性视网膜营养不良。这类患者由双等位RPE65突变的遗传性视网膜营养不良引起的视力丧失,其具有足够的活视网膜细胞。

Neurology:乳突骨瘤与高颅压1例

54岁,女性。进展性视力丧失和高催乳素血症的表现。

Ann R Coll Surg Engl:由筛鼻侵犯骨小梁的骨化纤维瘤造成单侧视力丧失的病例报告

英国诺里奇东英吉利大学的Ta NH等人近日在Ann R Coll Surg Engl杂志上发表了一篇病例报告,他们报告了一例鼻窦压迫右侧内侧的骨化纤维瘤,进而造成右侧视力损失的病例报告。