Extracellular Vesicles fromPRPF31+/−iPSC-Derived RPE Have a Distinct RNA Profile Compared to Those From Healthy RPE
bioRxiv (Cold Spring Harbor Laboratory)(2022)
摘要
Abstract Retinitis pigmentosa (RP) is the most common form of inherited retinal degeneration (IRD) and causes vision loss via dysfunction and death of the photoreceptor cells and retinal pigment epithelium (RPE) of the retina. Mutations in pre-mRNA processing factor 31 (PRPF31) are associated with autosomal dominant RP, and are thought to cause retinal degeneration by causing cell autonomous defects in RPE function. Genetic therapies such as adeno-associated virus (AAV) mediated gene therapy show great promise for treating IRDs, however in many cases it is challenging to measure clinical efficacy in a timely manner because IRDs progress slowly. A potential solution to this challenge is the use of additional outcome measures, such as biomarkers. Extracellular vesicles (EVs) are lipid enclosed vesicles that are secreted by cells and their RNA contents have been proposed as potential biomarkers in cancer and other diseases. We hypothesize EV RNAs can be used as biomarkers of the health status of the neural retina and RPE. To test this hypothesis for the RPE, we used PRPF31 +/+ and PRPF31 +/− human induced pluripotent stem cell (hiPSC)-derived RPE to investigate the RNAs contained in RPE-derived EVs, and how they change in disease. We also compared the RNA contents of RPE-EVs with the RNAs contained in the hiPSC-RPE cells themselves. We found that EVs from mutant PRPF31 +/− hiPSC-RPE cells contain distinct RNAs compared to EV from the control PRPF31 +/+ hiPSC-RPE cells, suggesting EV RNA contents change during disease and can potentially serve as biomarkers of retinal degeneration.
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关键词
extracellular vesicles,distinct rna profile,rpe,ipsc-derived
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