The RNA Content of Extracellular Vesicles from PRPF31+/- hiPSC-RPE Show Potential as Biomarkers of Retinal Degeneration
Getachew, H.; Mehrotra, S.; Fernandez-Godino, R.; Pierce, E. A.; Garita-Hernandez, M.
Show abstract
Retinitis pigmentosa (RP), is the most common inherited retinal degeneration (IRD), leading to vision loss via dysfunction and death of photoreceptor cells and retinal pigment epithelium (RPE). Mutations in the pre-mRNA processing factor 31 (PRPF31) gene are associated with autosomal dominant RP, impairing RPE function. While adeno-associated virus (AAV)-mediated gene therapy shows promise for treating IRDs, the slow progression of these diseases often makes timely measurement of clinical efficacy challenging. Extracellular vesicles (EVs) are lipid enclosed vesicles secreted by cells and their RNA contents are being explored as circulating biomarkers of cancer and other diseases. We hypothesize that EV RNAs could serve as biomarkers of the health status of the neural retina and RPE health. To test this, we used PRPF31+/+ and PRPF31+/- human-induced pluripotent stem cell (hiPSC)-derived RPE (hi-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 hi-RPE cells themselves. We found that EVs from mutant PRPF31+/- hi-RPE cells have distinct RNA profiles compared to those from control cells, suggesting EV RNA contents change during disease and could serve as biomarkers for retinal degeneration.
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