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Generation of Retinal Organoids from Healthy and Retinal Disease-Specific Human-Induced Pluripotent Stem Cells
Published on: December 9, 2022
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Generation and Staging of Human Retinal Organoids Based on Self-Formed Ectodermal Autonomous Multi-Zone System
Jinyan Li1, Yijia Chen1, Shuai Ouyang1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Frontiers in Cell and Developmental Biology
|October 11, 2021
Summary
This study presents a new method to create retinal organoids from stem cells without needing extra factors. These organoids mimic human eye development, generating mature cells and structures for disease modeling and drug discovery.
Area of Science:
- Biotechnology
- Developmental Biology
- Ophthalmology
Background:
- Stem cell-derived retinal organoids are valuable for modeling retinal diseases and drug screening.
- Existing methods often require exogenous factors, limiting their simplicity and robustness.
Purpose of the Study:
- To develop an exogenous-factors-free method for generating retinal organoids.
- To characterize the differentiation potential and long-term survival of these organoids.
- To establish a robust platform for retinogenesis research and translational applications.
Main Methods:
- Utilized the "self-formed ectodermal autonomous multi-zone" (SEAM) system for two-dimensional induction.
- Staged organoid differentiation into early and late phases.
- Employed 3D immunofluorescence and transmission electron microscopy for characterization.
- Co-suspended organoids with retinal pigment epithelium (RPE) to induce ciliary margin formation.
Main Results:
- Synchronous generation of multiple ocular cell lineages.
- Early phase differentiation yielded retinal ganglion cells, cone photoreceptors, amacrine cells, and horizontal cells.
- Late phase differentiation produced rod photoreceptors, bipolar cells, and Müller glial cells.
- Achieved long-term survival and demonstrated mature photoreceptors with outer segments and synapses.
- Induced functional RPE with distinct boundaries and observed ciliary margin formation.
Conclusions:
- The SEAM system provides a simple, robust, and exogenous-factors-free method for retinal organoid generation.
- The generated organoids accurately recapitulate key aspects of retinogenesis in vivo.
- This platform offers significant potential for studying retinal development, disease, and therapeutic applications.
