2. Academic Validation
  3. Aberrant Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem Cells of a Retinitis Pigmentosa Patient with the PRPF6 Mutation

Aberrant Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem Cells of a Retinitis Pigmentosa Patient with the PRPF6 Mutation

  • Int J Mol Sci. 2022 Aug 12;23(16):9049. doi: 10.3390/ijms23169049.
Yuqin Liang 1 2,  Feng Tan 1 2,  Xihao Sun 1 2,  Zekai Cui 1 2,  Jianing Gu 2,  Shengru Mao 2,  Hon Fai Chan 3 4,  Shibo Tang 1 2,  Jiansu Chen 1 2 5
Affiliations

Affiliations

  • 1 Aier School of Ophthalmology, Central South University, Changsha 410015, China.
  • 2 Aier Eye Institute, Changsha 410015, China.
  • 3 Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China.
  • 4 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China.
  • 5 Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China.
PMID: 36012314 DOI: 10.3390/ijms23169049
Abstract

Pre-mRNA processing factors (PRPFs) are vital components of the spliceosome and are involved in the physiological process necessary for pre-mRNA splicing to mature mRNA. As an important member, PRPF6 mutation resulting in autosomal dominant retinitis pigmentosa (adRP) is not common. Recently, we reported the establishment of an induced pluripotent stem cells (iPSCs; CSUASOi004-A) model by reprogramming the peripheral blood mononuclear cells of a PRPF6-related adRP patient, which could recapitulate a consistent disease-specific genotype. In this study, a disease model of retinal pigment epithelial (RPE) cells was generated from the iPSCs of this patient to further investigate the underlying molecular and pathological mechanisms. The results showed the irregular morphology, disorganized apical microvilli and reduced expressions of RPE-specific genes in the patient's iPSC-derived RPE cells. In addition, RPE cells carrying the PRPF6 mutation displayed a decrease in the phagocytosis of fluorescein isothiocyanate-labeled photoreceptor outer segments and exhibited impaired cell polarity and barrier function. This study will benefit the understanding of PRPF6-related RPE cells and future cell therapy.

Keywords

PRPF6; disease model; retinal pigment epithelium; retinitis pigmentosa.

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