Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications

Ion channels in retinal pigment epithelial (RPE) cells are crucial for retinal health and vision functions. Defects in such channels are intricately associated with the development of various retinopathies that cause blindness. Human pluripotent stem cells (hPSC)-derived RPE cells, including those from human-induced pluripotent stem cells (hiPSC) and human embryonic stem cells (hESC), have been used as in vitro models for investigating pathogenic mechanisms and screening potential therapeutic strategies for retinopathies. Therefore, the cellular status of hPSC-RPE cells, including maturity and physiologic functions, have been widely explored. Particularly, research on ion channels in hPSC-RPE cells can lead to the development of more stable models upon which robust investigations and clinical safety assessments can be performed. Moreover, the use of patient-specific hiPSC-RPE cells has significantly accelerated the clinical translation of gene therapy for retinal channelopathies, such as bestrophinopathies. This review consolidates current research on ion channels in hPSC-RPE cells, specifically Kir7.1, Bestrophin-1, CLC-2, and Ca_V1.3, providing a foundation for future research.