ePoster

Toward a comprehensive in vitro model of the human visual system: Three-dimensional assembloids integrating retinal and brain organoids

Ahmad Salti, Ammer-Pickhardt Franziska, Bellapianta Alessandro, Goureau Olivier, Bolz Matthias
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Ahmad Salti, Ammer-Pickhardt Franziska, Bellapianta Alessandro, Goureau Olivier, Bolz Matthias

Abstract

The intricate development of the visual system involves spatial and temporal coordination, especially the projection of retinal ganglion cell (RGC) axons to post-synaptic targets in the brain. Although retinal organoids (ROs) have mimicked retinal development, their limitations in modeling RGC projections prompted the creation of in vitro assembloids integrating retinal and brain organoids. This study aims to elucidate the projection patterns of the human visual system of inherited retinal dystrophy (IRD) subjects and how this might influence RGC development and survival while providing answers for prior challenges in RO cultures.iPSC derived from a very severe IRD subject, carrying PRPF31 mutation, were differentiated into ROs and cortical brain organoids following optimization of previously established protocols. The obtained organoids were incorporated at precise time points into assembloids forming a three-dimensional (3D) model of the visual system. RO and cortical brain organoids were successfully generated and the developed assembloids replicated the spatiotemporal organization of retinal organoids while overcoming previous limitations. RGCs exhibited enhanced survival, and their axons extended into brain-like tissues, mirroring the human visual system's projections. This innovative approach provides a more physiologically relevant system, offering insights into RGC development and pathfinding, as well as a platform for studying both IRD and neurodegenerative diseases.

Unique ID: fens-24/toward-comprehensive-vitro-model-human-d025fdaf