眼睛由屈光系统和视觉神经系统两大部分构成，是人体最重要的感觉器官之一。眼部各组织的发育或功能异常都可能造成不同程度的视力损害。目前主要通过动物实验或体外细胞培养的方法探究眼病的病理生理机制和治疗手段，但上述两种方法都存在一定的局限性。体外细胞培养不能完全反映器官的形态、结构和生化特征，而动物模型的物种和遗传背景具有异质性。近年来，随着原代组织、胚胎干细胞、诱导多能干细胞衍生的体外三维结构类器官和器官微流控芯片技术的不断发展，构建出了与在体器官的结构、功能更为相似的器官克隆模型，能够提供更敏感、定量、规模化的表型分析，更好地应用于眼的发育、生理结构、疾病机制、个性化医学诊断和治疗方法等方面的研究。目前，眼科的微流控器官芯片与类器官技术在角膜、晶状体、泪腺、视网膜结构发育和疾病模型均展现出巨大的应用潜力。
The eye is composed of refractive system and visual nervous system. It is one of the most important sensory organs of the human body. The abnormal development or function of eye tissues may cause various degrees of visual impairment. At present, the pathophysiological mechanism and treatment of eye diseases are mainly explored through animal experiments and in-vitro cell culture. However, they are of certain limitations. The in-vitro cell culture cannot fully reflect the morphological, structural and biochemical characteristics of organs, whereas the animal models are heterogeneous of species and genetic background. In recent years, with the continuous development of in-vitro three-dimensional structure organoids and organ microfluidic organ-on-a-chip technology derived from primary tissues, embryonic stem cells and induced pluripotent stem cells, organ cloning models more similar to in vivo organs in terms of the structure and function have been constructed. These models can provide more sensitive, quantitative and large-scale phenotypic analysis, and can be better applied to the research of eye development, physiological structure, disease mechanism, personalized medical diagnosis and treatment. At present, microfluidic organ-on-a-chip and organoids technologies have shown great application potential in the structural development and disease models’ construction of cornea, lens, lacrimal gland and retina.
视网膜退行性疾病的种类繁多、患病人口基数大，该病特征为终末期严重的视网膜细胞丢失。视网膜类器官(retinal organoid，RO)可通过3D干细胞体外分化培养技术大量获取，并拥有完整的各亚型视网膜细胞和经典的视网膜分层结构。因此，RO可作为最佳的视网膜退行性疾病建模方法之一，以便于发现潜在致病机制。目前，RO衍生物已被广泛用于视网膜细胞替代治疗的动物实验和临床研究，具体的成效参差不齐，可能的影响因素包括移植细胞数量、移植时间窗、移植工具等。随着RO相关研究的快速发展，视网膜退行性疾病在分子和个体上的诊断和治疗将进一步完善。
Retinal degenerative diseases, characterized by severe retinal cell loss at the end stage, are of various kinds and haunt vast amounts of patients. Retinal organoid (RO) with complete retinal cell subtypes and classic retinal stratification structures can be obtained in large quantities through stem cells in vitro 3D differentiation and culture method. Therefore, RO can serve as one of the best ways for retinal degenerative disease modeling to facilitate the decipherment of underlying pathogenic mechanisms. At present, RO derivatives have been widely used in animal experiments and clinical studies of retinal cell replacement therapy with varying results possibly affected by cell quantity, time window, or tools in terms of transplantation. With the booming progress of RO-related research, the diagnosis and treatment on molecular and individual level for retinal degenerative diseases will be further improved.
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.
