Capital Medical University, China (People's Republic)
Abstract: As the largest intraocular tissue, the vitreous occupies approximately 80% volume of the human eyeball and providing the eye with its spherical shape, a transparent light pathway as well as the homeostasis of intraocular humor. Reconstruction of the vitreous in vitro remains an unmet biomedical challenge. Here, through a stepwise differentiation from human pluripotent stem cells (hPSCs), we generated vitreous-like organoids (VOs) with vitreoretinal interface, displaying remarkable sameness to human vitreous in terms of transparency, molecular composition, biological profiles and transplantability. Using VOs as a developmental model, we revealed that fibroblasts, rather than vasculature, are essential for human vitreous development, thereby settling the longstanding debate in vitreous formation. Additionally, VOs with a transthyretin (TTR) mutation recapitulated the vitreous phenotypes of human patients with vitreous amyloidosis. Together, VOs open avenues to future studies of human vitreous development, disease modeling and regenerative therapy for a broad spectrum of human vitreoretinal diseases.
Funding Source: This project was supported by fundings from the National Natural Science Foundation of China (82125007,92368206), Beijing Natural Science Foundation (5242005, Z200014)
