Rossen Jennifer L, Williams Antionette L, Bohnsack Brenda L
Division of Ophthalmology, Ann and Robert H. Lurie Children's Hospital of Chicago , Chicago, IL, United States.
Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Front Cell Dev Biol. 2025 Mar 26;13:1552988. doi: 10.3389/fcell.2025.1552988. eCollection 2025.
Congenital cataracts are a leading cause of vision loss in children and can be an isolated finding or associated with systemic abnormalities. Isolated congenital cataracts are most commonly associated with pathogenic variants in one of the Crystallin genes. The α-Crystallins are small heat shock proteins that act as chaperones in the lens and other organs throughout the body to prevent protein aggregation and maintain tissue function. In contrast, the ß- and γ-Crystallins are structural proteins that are predominantly expressed in the mature lens and regulate its refractive index. However, the role of the Crystallins during lens development such that pathogenic variants result in inherited cataracts is less well-defined. As zebrafish allow real-time visualization of lens development, genetic manipulation of both the endogenous Crystallin genes as well as the use of transgenic overexpression of identified pathogenic variants yields important insight into the pathogenesis of congenital cataracts. Herein, we review the similarities and differences between human and zebrafish Crystallin genes. Further, we discuss the use of zebrafish as a model for congenital cataracts and explore the mechanisms that underlie the role of Crystallins in lens development. A better understanding of the genetic causes of congenital cataracts will lead to breakthroughs in preventing blindness from congenital cataracts and associated complications.
先天性白内障是儿童视力丧失的主要原因，可为孤立性发现或与全身异常相关。孤立性先天性白内障最常与晶状体蛋白基因之一的致病变异有关。α-晶状体蛋白是小热休克蛋白，在晶状体及全身其他器官中作为伴侣蛋白，防止蛋白质聚集并维持组织功能。相比之下，β-和γ-晶状体蛋白是结构蛋白，主要在成熟晶状体中表达并调节其折射率。然而，晶状体蛋白在晶状体发育过程中的作用，即致病变异导致遗传性白内障的机制，尚不太明确。由于斑马鱼可实时观察晶状体发育，对内源性晶状体蛋白基因进行基因操作以及对已鉴定的致病变异进行转基因过表达，有助于深入了解先天性白内障的发病机制。在此，我们综述了人类和斑马鱼晶状体蛋白基因的异同。此外，我们讨论了将斑马鱼作为先天性白内障模型的应用，并探讨了晶状体蛋白在晶状体发育中作用的潜在机制。更好地理解先天性白内障的遗传病因将有助于在预防先天性白内障及相关并发症导致的失明方面取得突破。
