Journal article
Generation of xenobiotic free retinofugal assembloids
Frontiers in cell and developmental biology, Vol.13, 1746709
01/01/2026
DOI: 10.3389/fcell.2025.1746709
PMID: 41613946
Abstract
Retinal ganglion cells (RGCs) are the output neurons of the retina, responsible for transmitting visual signals to the brain through the optic nerve. Their long axons, high metabolic demand, and the variable environments they transit make them particularly vulnerable to neurodegenerative insults in optic neuropathies. These insults include oxidative stress, excitotoxicity, and inflammatory damage, either within the neuroretina or within the optic nerve, and are thought to drive disease etiology. RGC-related vision loss is the primary presenting concern in many optic neuropathies including glaucoma and autoimmune demyelinating diseases such as multiple sclerosis MS-related optic neuritis (ON) is a result of immune-mediated damage to the myelinated optic nerve, a process not fully recapitulated in current in vitro organoid models. For instance, 3D organoid models offer improved architectural context, but they lack crucial cell types and sufficient anatomic complexity to mimic the in vivo environment. Further, widespread use of animal-derived reagents in these systems can introduce significant phenotype variability posing a major barrier to translational research. To address these challenges, retinofugal assembloid models have emerged. These models combine retinal and brain organoids to recapitulate the in vivo visual pathway, supporting RGC survival, RGC axonal extension and pathfinding, incorporation of additional glial cell types, and provide sufficient complexity. Here, we describe xenobiotic-free protocols for generating retinal and oligodendrocyte-rich cortical organoids and their fusion into assembloids to more accurately model RGC physiology. We discuss the advantages, limitations, and future applications of these systems in studying neuroinflammation and demyelination in a human-relevant context.
Details
- Title: Subtitle
- Generation of xenobiotic free retinofugal assembloids
- Creators
- Michael HayesMaria Valdes MichelMarkus KuehnRandy KardonOliver Gramlich
- Resource Type
- Journal article
- Publication Details
- Frontiers in cell and developmental biology, Vol.13, 1746709
- DOI
- 10.3389/fcell.2025.1746709
- PMID
- 41613946
- ISSN
- 2296-634X
- eISSN
- 2296-634X
- Publisher
- Frontiers Media SA; LAUSANNE
- Grant note
- Center for the Prevention and Treatment of Visual Loss Grant: 1I50RX003002-01 United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development ServiceNational Institute of Health: NEI R01EYE034194
The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Center for the Prevention and Treatment of Visual Loss Grant 1I50RX003002-01 from the United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service to RHK and MHK and by the National Institute of Health (NEI R01EYE034194) to OWG.
- Language
- English
- Date published
- 01/01/2026
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9985121499802771
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