Inherited cataracts: Genetic mechanisms and pathways new and old.
Inherited cataracts: Genetic mechanisms and pathways new and old.
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DOI：
10.1016/j.exer.2021.108662
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发表时间：
2021-08
影响因子：
3.4
通讯作者：
Hejtmancik JF
中科院分区：
文献类型：
--
作者：
Shiels A;Hejtmancik JF
白内障是透镜混浊的临床等价物，并且是由透镜细胞中的高分子量蛋白质聚集体或透镜微结构本身的破坏引起的光散射引起的。遗传性白内障背后的基因突变可以提供对透镜稳态和透明度至关重要的生物过程和途径的深入了解，经典地包括透镜晶体蛋白、连接蛋白、膜蛋白或组分以及中间丝蛋白。最近，白内障基因已经扩展到包括新鉴定的生物过程，例如伴侣或蛋白质降解组分、转录或生长因子、在透镜循环中有活性的通道以及胶原和细胞外基质组分。白内障可以按年龄分类，并且一般来说，先天性白内障是由严重突变引起的，导致对透镜蛋白质的重大损伤，而年龄相关的白内障与仅仅使蛋白质不稳定从而随时间增加对环境损害的易感性的变体有关。因此，先天性白内障和年龄相关性白内障的混浊可能存在不同的途径，其中先天性白内障诱导未折叠蛋白反应（UPR）和细胞凋亡以破坏透镜微结构，而在年龄相关性白内障中，由α-晶状体蛋白结合的变性晶状体蛋白形成的高分子量（HMW）聚集体导致光散射，而不会严重损害透镜微结构。
Cataract(s) is the clinical equivalent of lens opacity and is caused by light scattering either by high molecular weight protein aggregates in lens cells or disruption of the lens microarchitecture itself. Genetic mutations underlying inherited cataract can provide insight into the biological processes and pathways critical for lens homeostasis and transparency, classically including the lens crystallins, connexins, membrane proteins or components, and intermediate filament proteins. More recently, cataract genes have been expanded to include newly identified biological processes such as chaperone or protein degradation components, transcription or growth factors, channels active in the lens circulation, and collagen and extracellular matrix components. Cataracts can be classified by age, and in general congenital cataracts are caused by severe mutations resulting in major damage to lens proteins, while age related cataracts are associated with variants that merely destabilize proteins thereby increasing susceptibility to environmental insults over time. Thus there might be separate pathways to opacity for congenital and age-related cataracts whereby congenital cataracts induce the unfolded protein response (UPR) and apoptosis to destroy the lens microarchitecture, while in age related cataract high molecular weight (HMW) aggregates formed by denatured crystallins bound by α-crystallin result in light scattering without severe damage to the lens microarchitecture.
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影响因子：
3.4
作者：
McGreal RS;Brennan LA;Kantorow WL;Wilcox JD;Wei J;Chauss D;Kantorow M
通讯作者：
Kantorow M
影响因子：
3.4
作者：
Brennan LA;McGreal-Estrada R;Logan CM;Cvekl A;Menko AS;Kantorow M
通讯作者：
Kantorow M
影响因子：
9.8
作者：
Billingsley, Gail;Santhiya, Sathiyavedu T.;Heon, Elise
通讯作者：
Heon, Elise
影响因子：
2
作者：
Boone, Philip M.;Yuan, Bo;Lewis, Richard A.
通讯作者：
Lewis, Richard A.
影响因子：
4.4
作者：
Benito, Antonio;Hervella, Lucia;Artal, Pablo
通讯作者：
Artal, Pablo