Ikkala Kaisa, Raatikainen Sini, Koivula Henri, Michon Frederic
Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Zebrafish Unit, HiLIFE, University of Helsinki, Helsinki, Finland.
Front Physiol. 2022 Nov 1;13:906155. doi: 10.3389/fphys.2022.906155. eCollection 2022.
Corneal blindness is the fourth leading cause of blindness worldwide. The superficial position of cornea on the eye makes this tissue prone to environmental aggressions, which can have a strong impact on sight. While most corneal pathology studies utilize terrestrial models, the knowledge on zebrafish cornea is too scarce to comprehend its strategy for the maintenance of a clear sight in aquatic environment. In this study, we deciphered the cellular and molecular events during corneal formation and maturation in zebrafish. After describing the morphological changes taking place from 3 days post fertilization (dpf) to adulthood, we analyzed cell proliferation. We showed that label retaining cells appear around 14 to 21dpf. Our cell proliferation study, combined to the study of and expression, demonstrate a long maturation process, ending after 45dpf. This maturation ends with a solid patterning of corneal innervation. Finally, we demonstrated that corneal wounding leads to an intense dedifferentiation, leading to the recapitulation of corneal formation and maturation, a plasticity period. Altogether, our study deciphers the maturation steps of an aquatic cornea. These findings demonstrate the conservation of corneal formation, maturation and wound healing process in aquatic and terrestrial organisms, and they will enhance the use of zebrafish as model for corneal physiology studies.
角膜盲是全球第四大致盲原因。角膜在眼睛上的浅表位置使该组织容易受到环境侵害,这可能对视力产生重大影响。虽然大多数角膜病理学研究使用陆地模型,但关于斑马鱼角膜的知识非常稀少,难以理解其在水生环境中维持清晰视力的策略。在本研究中,我们解读了斑马鱼角膜形成和成熟过程中的细胞和分子事件。在描述了从受精后3天(dpf)到成年期发生的形态变化后,我们分析了细胞增殖。我们发现标记保留细胞在14至21dpf左右出现。我们的细胞增殖研究,结合对[此处原文缺失相关基因名称]表达的研究,表明角膜成熟过程漫长,在45dpf后结束。这种成熟以角膜神经支配的稳固模式结束。最后,我们证明角膜损伤会导致强烈的去分化,从而重现角膜的形成和成熟,即一个可塑性时期。总之,我们的研究解读了水生角膜的成熟步骤。这些发现证明了水生和陆地生物在角膜形成、成熟和伤口愈合过程中的保守性,并且它们将增强斑马鱼作为角膜生理学研究模型的应用。