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：

视网膜疾病的多能干细胞来源模型：阐明发病机制、评估新疗法和估计毒性

失明构成了日益严峻的全球挑战，大约 26% 的病例归因于退行性视网膜疾病。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，但这些高成本疗法只会使少数患者受益。因此，了解视网膜疾病是推进有效治疗的关键，需要复制病理学的模型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，因为它们具有无限的供应和分化为包含所有细胞类型的光响应视网膜组织的能力。本文重点介绍 PSC 生成光感受器和视网膜色素上皮（RPE）细胞的历史和现状。我们探索了这项技术在疾病建模、实验性治疗测试、生物标志物鉴定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，并强调了将脉管系统和免疫细胞整合到视网膜类器官中的重要性。我们倡导在数据采集和分析中实现高通量自动化，并强调完全捕获神经视网膜、RPE 和脉络膜毛细血管之间相互作用的先进微生理系统的价值。

更新日期：2024-02-16

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