Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids

• DOI: 10.1016/j.stemcr.2022.02.019
• Publication Date: 2022-03-25T03:06:41Z
• Authors: Emma L. West; Paromita Majumder; Arifa Naeem; Milan Fernando; Michelle O'Hara-W...; Emily Lanning; Magdalena Kloc; Joana Ribeiro; Patrick Ovando-Roche; Ian O. Shum; Neeraj Jumbu; Robert Sampson; Matt Hayes; James W.B. Bainbr...; Anastasios Georgi...; Alexander J. Smith; Anai Gonzalez-Cor...; Robin R. Ali
• Keywords: Organoid; Retinal Disorder; Visual phototransduction

The generation of retinal organoids from human pluripotent stem cells (hPSC) is now a well-established process that in part recapitulates development. However, hPSC-derived photoreceptors exhibit well-organized outer segment structures have yet to be observed. To facilitate improved inherited disease modeling, we determined conditions would support development maturing photoreceptors. We established the use antioxidants and BSA-bound fatty acids promotes formation membranous segment-like structures. Using new protocols for organoid culture, demonstrated both rod cone photoreceptors, including organized stacked discs. these enhanced generate iPSC-derived patients with X-linked retinitis pigmentosa, robust cellular phenotypes could ameliorated following adeno-associated viral vector-mediated gene augmentation. These findings should aid modeling therapeutic approaches treatment photoreceptor disorders.