Retinal cytoarchitecture is preserved in an organotypic perfused human and porcine eye model.

IF 6.2 2区 医学 Q1 NEUROSCIENCES
Darren Chan, Jenny Wanyu Zhang, Gah-Jone Won, Jeremy M Sivak
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引用次数: 0

Abstract

Pathobiology of the intact human retina has been challenging to study due to its relative inaccessibility and limited sample availability. Thus, there is a great need for new translational models that can maintain human retinal integrity and cytoarchitecture. The role of physiologic intraocular pressure (IOP) and fluid flow on retinal tissue has not been well studied. Here, we present an ex vivo organotypic model to assess the impact of physiological intraocular perfusion on retinal cytoarchitecture and cell survival. We demonstrate that retinal cytoarchitecture is remarkably well preserved following re-establishment of physiological IOP and aqueous humor dynamics for up to 24 h in ex vivo whole globe porcine and human eyes, comparable to freshly preserved control eyes. Accordingly, cell death was minimized in the perfused retinas, which also displayed normal markers of cellular metabolism and astrogliosis. These results are in marked contrast to contralateral control eyes without active perfusion, which displayed excessive cell death and disrupted cytoarchitecture at the same time point. These experiments demonstrate the critical impact that physiological pressure and fluid flow have on retinal tissue, and introduce a new pre-clinical model to study human and porcine retinal health and degeneration in a relevant biomechanical setting.

视网膜细胞结构在器官型灌注人眼和猪眼模型中得以保存。
完整人视网膜的病理生物学研究一直具有挑战性,由于其相对难以接近和有限的样本可用性。因此,有很大的需要新的翻译模型,可以维持人类视网膜的完整性和细胞结构。生理性眼内压(IOP)和液体流动对视网膜组织的作用尚未得到很好的研究。在这里,我们提出了一个体外器官型模型来评估生理眼内灌注对视网膜细胞结构和细胞存活的影响。我们证明,在离体猪和人的眼睛中,在生理IOP和房水动力学重建长达24小时后,视网膜细胞结构得到了非常好的保存,与新鲜保存的对照眼睛相当。因此,灌注视网膜的细胞死亡最小,细胞代谢和星形胶质细胞形成也显示正常。这些结果与没有主动灌注的对侧对照眼形成鲜明对比,后者在同一时间点表现出过度的细胞死亡和细胞结构破坏。这些实验证明了生理压力和流体流动对视网膜组织的重要影响,并在相关的生物力学环境下引入了一种新的临床前模型来研究人类和猪的视网膜健康和变性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta Neuropathologica Communications
Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine
CiteScore
11.20
自引率
2.80%
发文量
162
审稿时长
8 weeks
期刊介绍: "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.
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