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Updated: Sep 15, 2025
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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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Modeling human retinal ganglion cell axonal outgrowth, development, and pathology using pluripotent stem cell-based
Cátia Gomes1,2, Kang-Chieh Huang2,3, Sailee S Lavekar2,3
1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202.
Biorxiv : the Preprint Server for Biology
|July 14, 2025
Summary
Researchers developed a novel microfluidic platform to study retinal ganglion cells (RGCs) in health and disease. This model revealed axonal deficits in glaucoma and showed how astrocyte reactivity drives RGC neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Ophthalmology
Background:
- Retinal ganglion cells (RGCs) are crucial for vision, connecting the eye to the brain via long axons.
- RGC degeneration occurs compartmentally, affecting axons and cell bodies differently in disease.
- Existing models struggle to replicate RGC compartmentalization and disease-specific responses.
Purpose of the Study:
- To develop a microfluidic platform for analyzing RGC compartmentalization in health and disease.
- To investigate RGC responses to glaucoma mutations and astrocyte interactions in vitro.
- To create a more physiologically relevant model for studying RGC neurodegeneration.
Main Methods:
- Utilized microfluidic chips to culture human pluripotent stem cell (hPSC)-derived RGCs, isolating axons from somatodendritic compartments.
- Compared RGCs with and without the OPTN(E50K) glaucoma mutation, analyzing axonal outgrowth, transport, and transcriptome.
- Incorporated astrocytes into the microfluidic model to study their role in RGC degeneration.
Main Results:
- The microfluidic platform successfully cultured hPSC-RGCs, promoting axonal growth and compartmentalization.
- Patient-specific RGCs carrying the glaucoma mutation showed impaired axonal outgrowth and reduced axonal transport.
- Inducing astrocyte reactivity in proximity to RGC axons triggered neurodegenerative phenotypes.
Conclusions:
- The microfluidic system effectively recapitulates RGC compartmentalization and disease pathology in vitro.
- This platform provides a novel, physiologically relevant model for studying RGC development and neurodegeneration.
- Findings highlight the role of axonal deficits and astrocyte reactivity in glaucoma and RGC degeneration.
