ArticleNature communications2022
HBEGF-TNF induce a complex outer retinal pathology with photoreceptor cell extrusion in human organoids.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution.Nature communications · 2026Article
- Single-cell analysis reveals impaired Müller glia-mediated intercellular communication and photoreceptor pathology in USH1C retinal organoids.Cellular and molecular life sciences : CMLS · 2026Article
- Current Advances and Applications of Retinal Organoids.Neuroscience bulletin · 2026Review
- Engineering Human Retinal Organoids and Eye-on-a-Chip Models for Degenerative Eye Disease.ACS biomaterials science & engineering · 2026Review
- Longitudinal analysis of retinal cell state transitions in RB1-deficient retinal organoids reveals the nascent cone precursors are the earliest cell-origin of human retinoblastoma.Cell death & disease · 2026Article
- Early downregulation of hair cell (HC)-specific genes in the vestibular sensory epithelium during chronic ototoxicity.Journal of biomedical science · 2025Article
- 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as DInternational journal of molecular sciences · 2025Article
- DNA Origami Barcodes for Immunostaining.ACS applied materials & interfaces · 2025Article
- Stratification of the Extent of Visual Impairment Identifies Sex-Specific Degenerative Changes in Retinal Structure and Function during Aging.Journal of integrative neuroscience · 2025Article
- Editorial: Celebrating the year of Ramon y Cajal: cellular biology of the retina.Frontiers in cellular neuroscience · 2025Article
- Review
- Live Imaging Microscopy of Human Retina Organoids: Photoreceptor Pathology.Advances in experimental medicine and biology · 2025Review
- Piezo in the eye: expression, distribution and roles in ocular diseases.Frontiers in physiology · 2025Review
- Inceptor binds to and directs insulin towards lysosomal degradation in β cells.Nature metabolism · 2024Article
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- Modeling complex age-related eye disease.Progress in retinal and eye research · 2024Review
- Advanced 3D imaging and organoid bioprinting for biomedical research and therapeutic applications.Advanced drug delivery reviews · 2024Review
- The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex.The EMBO journal · 2024Article
- Age-Related Macular Degeneration, a Mathematically Tractable Disease.Investigative ophthalmology & visual science · 2024Review
- Toward Retinal Organoids in High-Throughput.Cold Spring Harbor perspectives in medicine · 2024Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human organoids could facilitate research of complex and currently incurable neuropathologies, such as age-related macular degeneration (AMD) which causes blindness. Here, we establish a human retinal organoid system reproducing several parameters of the human retina, including some within the macula, to model a complex combination of photoreceptor and glial pathologies. We show that combined application of TNF and HBEGF, factors associated with neuropathologies, is sufficient to induce photoreceptor degeneration, glial pathologies, dyslamination, and scar formation: These develop simultaneously and progressively as one complex phenotype. Histologic, transcriptome, live-imaging, and mechanistic studies reveal a previously unknown pathomechanism: Photoreceptor neurodegeneration via cell extrusion. This could be relevant for aging, AMD, and some inherited diseases. Pharmacological inhibitors of the mechanosensor PIEZO1, MAPK, and actomyosin each avert pathogenesis; a PIEZO1 activator induces photoreceptor extrusion. Our model offers mechanistic insights, hypotheses for neuropathologies, and it could be used to develop therapies to prevent vision loss or to regenerate the retina in patients suffering from AMD and other diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.