Wang Joyce, Nnoromele Patrick O, Liu Ying V, Johnston Robert J, Singh Mandeep S
University of Maryland School of Medicine, Baltimore, MD, USA.
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Prog Retin Eye Res. 2025 Jan;104:101317. doi: 10.1016/j.preteyeres.2024.101317. Epub 2024 Nov 16.
Photoreceptor transplantation is a potential therapeutic strategy for degenerative retinal diseases. Studies on mechanisms contributing to retinal regeneration and vision repair identified cellular components transfer (CCT) as playing a role, in addition to somatic augmentation (referred to as "cell replacement" in this paper). In CCT, donor photoreceptors shuttle proteins, RNA, and mitochondria to host photoreceptors through intercellular connections. The discovery of CCT in the transplantation context triggered a re-interpretation of prior transplantation studies that generally did not include specific CCT assays and thereby broadly emphasized the cell replacement model, reflecting the prevailing understanding of retinal transplantation biology at that time. In addition to clarifying our understanding of photoreceptor biology, CCT has raised the possibility of developing treatments to replenish molecular deficiencies in diseased photoreceptor cells. As the CCT field evolves, investigators have used diverse terminology, and implemented different CCT assays following transplantation in animal models. The non-standardized terminology of CCT and absent minimal assay standards for detection can hinder communication between investigators and comparison between studies. In this review, we discuss the current understanding of CCT, provide an overview of transplantation and regeneration studies in small and large animals, and propose terminology and a minimal assay standard for CCT. Further research on CCT may eventually provide new avenues to treat a range of hereditary and acquired retinopathies while illuminating mechanisms of cell-cell interaction in the retina.
光感受器移植是治疗视网膜退行性疾病的一种潜在策略。对视网膜再生和视力修复机制的研究表明,除了体细胞增强(本文中称为“细胞替代”)外,细胞成分转移(CCT)也发挥了作用。在CCT过程中,供体光感受器通过细胞间连接将蛋白质、RNA和线粒体传递给宿主光感受器。在移植背景下CCT的发现引发了对先前移植研究的重新解读,这些研究通常没有包括特定的CCT检测,因此广泛强调细胞替代模型,反映了当时对视网膜移植生物学的普遍理解。除了阐明我们对光感受器生物学的理解外,CCT还提出了开发治疗方法以补充患病光感受器细胞分子缺陷的可能性。随着CCT领域的发展,研究人员使用了不同的术语,并在动物模型移植后实施了不同的CCT检测。CCT的非标准化术语以及缺乏最低检测标准可能会阻碍研究人员之间的交流以及研究之间的比较。在这篇综述中,我们讨论了对CCT的当前理解,概述了小型和大型动物的移植和再生研究,并提出了CCT的术语和最低检测标准。对CCT的进一步研究最终可能会为治疗一系列遗传性和获得性视网膜病变提供新途径,同时阐明视网膜中细胞间相互作用的机制。