Eyestem Research Private Limited, Centre for Cellular and Molecular Platforms (CCAMP), National Centre for Biological Sciences-Tata Institute of Fundamental Research (NCBS-TIFR), GKVK Campus, Bangalore, 560065, India.
Eyestem Research Private Limited, Centre for Cellular and Molecular Platforms (CCAMP), National Centre for Biological Sciences-Tata Institute of Fundamental Research (NCBS-TIFR), GKVK Campus, Bangalore, 560065, India; Centre for Eye Genetics and Research, Cytecare Hospital, Bellary Road, Bangalore, 560064, India.
J Chem Neuroanat. 2019 Jan;95:81-88. doi: 10.1016/j.jchemneu.2018.02.002. Epub 2018 Feb 12.
Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction, lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies. We also provide an overview of the ongoing efforts towards developing a suitable in vitro model for modeling retinal degenerative diseases. This basic understanding in turn has contributed to advances in translational goals such as drug screening and cell-replacement therapies. Furthermore we discuss gene editing approaches for autologous repair of genetic disorders and allogeneic transplantation of stem cell-based retinal derivatives for degenerative disorders with an ultimate goal to restore vision. It is pertinent to note however, that these exciting new developments throw up several challenges that need to be overcome before their full clinical potential can be realized.
视网膜退行性疾病是遗传性、不可逆和不可治愈的视力丧失的主要原因。虽然各种啮齿动物模型系统在这方面提供了重要信息，但缺乏与疾病相关的组织可用性和物种特异性差异已被证明是一个主要障碍。人类诱导多能干细胞（iPSC）不仅在理解疾病机制方面，而且在潜在的治疗方法方面都为治愈疾病开辟了全新的可能性。在这篇综述中，我们总结了从 iPSC 中衍生视网膜细胞类型的最新方法进展，这些方法可以作为基本和转化研究中与疾病相关的细胞群体的可再生来源。我们还概述了为建立用于模拟视网膜退行性疾病的合适体外模型而正在进行的努力。这种基本理解反过来又促进了转化目标的进展，如药物筛选和细胞替代疗法。此外，我们还讨论了用于基因编辑的自体修复遗传疾病和同种异体移植基于干细胞的视网膜衍生物的方法，以恢复视力为最终目标。然而，值得注意的是，这些令人兴奋的新发展带来了几个挑战，需要在充分实现其临床潜力之前克服这些挑战。
