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Updated: Jan 6, 2026
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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.
Summary
A new microfluidic platform allows researchers to study retinal ganglion cells (RGCs) in health and disease. This human-specific model reveals compartment-specific neurodegeneration in glaucoma and highlights axon-glia interactions.
Area of Science:
- Neuroscience
- Cell Biology
- Ophthalmology
Background:
- Retinal ganglion cells (RGCs) are crucial neurons connecting the eye to the brain.
- RGC degeneration in disease and injury occurs in distinct axonal and somatodendritic compartments.
- Understanding these regional differences is key to developing effective treatments.
Purpose of the Study:
- To develop a microfluidic platform for studying RGC compartmentalization in health and disease.
- To investigate compartment-specific neurodegenerative mechanisms in glaucoma.
- To explore the role of glial cells in RGC axonal health.
Main Methods:
- Human pluripotent stem cell (hPSC)-derived RGCs were cultured in microfluidic devices enabling axonal and somatodendritic separation.
- Compartment-specific phenotypes of RGCs with the OPTN(E50K) glaucoma mutation were analyzed.
- Axonal RNA-sequencing and co-culture models with astrocytes were employed.
Main Results:
- The microfluidic platform successfully segregated RGC axons and somatodendrites.
- OPTN-mutant RGCs exhibited reduced axon length and impaired axonal transport.
- Transcriptomic analysis revealed disease-specific alterations in OPTN axons.
- Diseased astrocytes induced compartment-specific neurodegeneration in RGCs.
Conclusions:
- The developed microfluidic platform is a physiologically relevant, human-specific in vitro system for studying RGCs.
- This model recapitulates spatial features of RGCs in health and disease.
- The platform facilitates research into neuronal development, axon-glia interactions, and neurodegeneration mechanisms.
