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视网膜退行性疾病的细胞治疗:进展与展望

Cell Therapy for Retinal Degenerative Diseases: Progress and Prospects.

作者信息

Wu Kevin Y, Dhaliwal Jaskarn K, Sasitharan Akash, Kalevar Ananda

机构信息

Department of Surgery, Division of Ophthalmology, University of Sherbrooke, Sherbrooke, QC J1G 2E8, Canada.

Faculty of Health Sciences, Department of Medicine, Queen's University, Kingston, ON K7L 3N6, Canada.

出版信息

Pharmaceutics. 2024 Oct 5;16(10):1299. doi: 10.3390/pharmaceutics16101299.

Abstract

Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are leading causes of vision loss, with AMD affecting older populations and RP being a rarer, genetically inherited condition. Both diseases result in progressive retinal degeneration, for which current treatments remain inadequate in advanced stages. This review aims to provide an overview of the retina's anatomy and physiology, elucidate the pathophysiology of AMD and RP, and evaluate emerging cell-based therapies for these conditions. A comprehensive review of the literature was conducted, focusing on cell therapy approaches, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells. Preclinical and clinical studies were analyzed to assess therapeutic potential, with attention to mechanisms such as cell replacement, neuroprotection, and paracrine effects. Relevant challenges, including ethical concerns and clinical translation, were also explored. Cell-based therapies demonstrate potential for restoring retinal function and slowing disease progression through mechanisms like neuroprotection and cell replacement. Preclinical trials show promising outcomes, but clinical studies face significant hurdles, including challenges in cell delivery and long-term efficacy. Combination therapies integrating gene editing and biomaterials offer potential future advancements. While cell-based therapies for AMD and RP have made significant progress, substantial barriers to clinical application remain. Further research is essential to overcome these obstacles, improve delivery methods, and ensure the safe and effective translation of these therapies into clinical practice.

摘要

年龄相关性黄斑变性(AMD)和视网膜色素变性(RP)是导致视力丧失的主要原因,其中AMD影响老年人群,而RP是一种较为罕见的遗传性疾病。这两种疾病都会导致视网膜进行性变性,目前针对晚期阶段的治疗方法仍然不足。本综述旨在概述视网膜的解剖学和生理学,阐明AMD和RP的病理生理学,并评估针对这些病症的新兴细胞疗法。我们对文献进行了全面综述,重点关注细胞治疗方法,包括胚胎干细胞(ESC)、诱导多能干细胞(iPSC)、间充质干细胞(MSC)和视网膜祖细胞。分析了临床前和临床研究以评估治疗潜力,同时关注细胞替代、神经保护和旁分泌效应等机制。还探讨了相关挑战,包括伦理问题和临床转化。基于细胞的疗法通过神经保护和细胞替代等机制显示出恢复视网膜功能和减缓疾病进展的潜力。临床前试验显示出有前景的结果,但临床研究面临重大障碍,包括细胞递送和长期疗效方面的挑战。整合基因编辑和生物材料的联合疗法有望在未来取得进展。虽然针对AMD和RP的基于细胞的疗法已经取得了重大进展,但临床应用仍存在重大障碍。进一步的研究对于克服这些障碍、改进递送方法以及确保这些疗法安全有效地转化为临床实践至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391e/11510658/c6bdb2982725/pharmaceutics-16-01299-g001.jpg

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