先天性白内障是晶状体发育异常引起的以晶状体混浊为特征的疾病，导致婴幼儿中重度视力损害，严重影响患儿长期生存质量，给全球带来较大的社会经济负担。目前先天性白内障的发病机制尚未得到很好的阐明，遗传因素虽在其中扮演重要角色，但已知基因突变仅能解释约30%的病例，大多数患儿发病原因仍不明确。晶状体的透明性依赖于晶状体上皮细胞和纤维细胞精密有序的排列，这与受到严格调控的晶状体发育过程密切相关，任何环节异常均可能导致晶状体早期混浊。故阐明调控晶状体发育的分子与细胞机制，是深入探究先天性白内障病因的前提。表观遗传学是在DNA序列不改变的情况下，对控制基因的活性和表达的因素进行研究的学科，包括DNA甲基化、组蛋白修饰、染色质重塑、非编码RNA调控等多种修饰，近年受到生命科学领域研究者较多的关注。在眼发育及眼部各类疾病机制探索中，表观遗传调控已被证实参与多种生理与病理过程。本综述通过总结已发表的与晶状体发育和先天性白内障发病机制相关的表观遗传学研究，尝试汇总与先天性白内障发生发展相关的表观遗传分子及通路，为进一步揭示疾病机制提供理论依据，并为未来的临床诊疗提供新的思路和方法。
Congenital cataract is a disease characterized by lens opacity due to abnormal lens development.This opacity results in moderate to severe visual impairment in infants and young children, significantly impacting their long-term quality of life and imposing a substantial socioeconomic burden globally. The pathogenesis of congenital cataract remains not fully understood. Although genetic factors play a significant role, known gene mutations account for only about 30% of cases, leaving the underlying cause unclear for the majority of affected children. Lens transparency depends on the precise, ordered arrangement of lens epithelial cells and fiber cells, a process that is closely tied to the strictly regulated lens development. Abnormalities at any stage of development may lead to early lens opacity. Therefore, clarifying the molecular and cellular mechanisms that regulate lens development is a prerequisite for investigating the etiology of congenital cataract. Epigenetics is the field of study that focuses on factors controlling gene activity and expression without altering DNA sequences. It encompasses a wide range of modifications including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation, and has garnered significant attention from researchers in recent years. In the context of ocular development and the mechanisms underlying various eye diseases, epigenetic regulation has been shown to participate in multiple physiological and pathological processes. This review synthesizes published research on epigenetics related to lens development and the pathogenesis of congenital cataract. It aims to summarize the epigenetic molecules and pathways associated with the onset and progression of congenital cataracts, providing a theoretical foundation for further elucidating disease mechanisms and offering new insights and approaches for future clinical diagnosis and treatment.
眼睛是人体最重要的感觉器官之一，主要由角膜和晶状体构成的屈光系统和视网膜构成的视觉神经系统2个部分构成。眼睛各组织的发育和功能异常都可影响视功能，甚至致盲。现有的致盲眼病的治疗方式均存在各自瓶颈问题，新的诊治方法亟待开发。近年来，得益于干细胞和组织工程学的发展，结合现有眼各组织的发育理论知识，研究者们利用多种来源的干细胞在体外成功诱导出具有组织特异结构和功能的眼类器官。眼类器官研究为利用干细胞研究眼组织发育和眼病发病机制、药物筛选以及替代治疗创造了新机遇，将干细胞治疗眼病的转化研究推向了一个更高平台。本文将对现有眼类器官的技术发展及应用进行综述。
Being one of the most important sensory organs, the eye is composed of the cornea, the lens, which are responsible for refraction, and the retina, which is the neural sensory part of the eye. Various kinds of developmental abnormalities and functional defects could lead to visual dysfunctions, and even blindness. Current treatments for blindness-causing eye diseases all have their own limitations, awaiting new efficient diagnostic and treating methods. Thanks to the development in stem cell biology and bioengineering, taking advantage of the rich knowledge accumulated on the mechanisms governing eye development, researchers have successfully generated various ocular organoids using multiple sources of stem cells in vitro, which resemble their counterparts in vivo on both the structural level and functional level. Ocular organoids provide valuable material and models for studying eye development, pathology, drug screening, and cell replacement therapy, pushing translational studies of ocular stem cell to a new era. Here, the paper reviews the development and application of ocular organoid technologies.
