Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity,Progress in Retinal and Eye Research

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Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity
Progress in Retinal and Eye Research ( IF 18.6 ) Pub Date : 2024-02-16 , DOI: 10.1016/j.preteyeres.2024.101248
Marzena Kurzawa-Akanbi ₁ , Nikolaos Tzoumas ₁ , Julio C Corral-Serrano ₂ , Rosellina Guarascio ₂ , David H Steel ₁ , Michael E Cheetham ₂ , Lyle Armstrong ₁ , Majlinda Lako ₁

Affiliation

Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and retinal prostheses offer hope for vision restoration, these high-cost therapies will benefit few patients. Understanding retinal diseases is therefore key to advance effective treatments, requiring models replicating pathology and allowing quantitative assessments for drug discovery. Pluripotent stem cells (PSCs) provide a unique solution given their limitless supply and ability to differentiate into light-responsive retinal tissues encompassing all cell types. This review focuses on the history and current state of photoreceptor and retinal pigment epithelium (RPE) cell generation from PSCs. We explore the applications of this technology in disease modelling, experimental therapy testing, biomarker identification, and toxicity studies. We consider challenges in scalability, standardisation, and reproducibility, and stress the importance of incorporating vasculature and immune cells into retinal organoids. We advocate for high-throughput automation in data acquisition and analyses and underscore the value of advanced micro-physiological systems that fully capture the interactions between the neural retina, RPE, and choriocapillaris.

中文翻译：

多能干细胞衍生的视网膜疾病模型：阐明发病机制、评估新疗法并估计毒性

失明是一个日益严重的全球性挑战，大约 26% 的失明病例归因于视网膜退行性疾病。虽然基因疗法、光遗传学工具、光敏开关和视网膜假体为视力恢复带来了希望，但这些高成本的疗法只会让少数患者受益。因此，了解视网膜疾病是推进有效治疗的关键，需要模型复制病理学并允许对药物发现进行定量评估。多能干细胞 (PSC) 提供了一种独特的解决方案，因为它们的供应量无限，并且能够分化为包含所有细胞类型的光响应性视网膜组织。本综述重点介绍 PSC 产生光感受器和视网膜色素上皮 (RPE) 细胞的历史和现状。我们探索该技术在疾病建模、实验治疗测试、生物标志物识别和毒性研究中的应用。我们考虑了可扩展性、标准化和可重复性方面的挑战，并强调将脉管系统和免疫细胞纳入视网膜类器官的重要性。我们提倡数据采集和分析中的高通量自动化，并强调先进的微生理系统的价值，该系统可以充分捕获神经视网膜、RPE 和脉络膜毛细血管之间的相互作用。

更新日期：2024-02-16

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