Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells

Front Med (Lausanne). 2024 Jul 1:11:1328474. doi: 10.3389/fmed.2024.1328474. eCollection 2024.

Abstract

Since the discovery of induced pluripotent stem cell (iPSC) technology, there have been many attempts to create cellular models of inherited retinal diseases (IRDs) for investigation of pathogenic processes to facilitate target discovery and validation activities. Consistency remains key in determining the utility of these findings. Despite the importance of consistency, quality control metrics are still not widely used. In this review, a toolkit for harnessing iPSC technology to generate photoreceptor, retinal pigment epithelial cell, and organoid disease models is provided. Considerations while developing iPSC-derived IRD models such as iPSC origin, reprogramming methods, quality control metrics, control strategies, and differentiation protocols are discussed. Various iPSC IRD models are dissected and the scientific hurdles of iPSC-based disease modeling are discussed to provide an overview of current methods and future directions in this field.

Keywords: induced pluripotent stem cell; inherited retinal diseases; organoids; photoreceptor cells; retinal pigment epithelium.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Clinician Scientist Award (CSA) grant titled Thermogel Enhanced Retinal Cell Therapy for Age-Related Retinal Degenerative Disease (MOH-001106, WBS A-8000773-00-00). The grant is awarded by the National Medical Research Council (NMRC), Singapore.