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NCT Number: NCT07688538

Mapping of the Developmental Atlas of the Visual System and Research on Embryonic Neurogenesis Phenomena

This research studies how nerve cells in the human embryonic retina, visual brain regions, and brain areas responsible for higher cognitive functions grow, develop, and form interconnected functional networks.

Eye tissue, visual brain tissue, and other brain tissue linked to advanced cognitive functions will be collected from embryos whose pregnancies were terminated due to medical conditions or illnesses. High-throughput single-cell and single-nucleus sequencing will be utilized to map gene activity patterns and developmental growth pathways of retinal nerve cells.

Multiple testing tools will be combined to analyze these brain and retinal cells: Patch-seq (single-cell patch-clamp sequencing), high-density microelectrode arrays (MEA), and two-photon calcium imaging. With these tools, systematic measurements will be performed on the electrical activity, physical shape, synaptic connection patterns, and signal coding functions of neurons in the retina and visual brain regions. Multi-modal tissue maps and a public database will be constructed to store all collected research data.

Immunofluorescence staining will also be applied to compare structural differences and nerve fiber connections between visual brain regions and higher cognitive brain areas. The regenerative capacity and neuron formation process of embryonic brain stem cells, as well as the migration paths of developing neurons, will be tracked.

Overall, this study aims to fully uncover the neural foundation of visual signal processing, and identify the molecular regulatory networks that control nerve tissue development during the embryonic stage.

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Key information

Conditions

Embryonic Development Neural Development Retinal Anomalies

Sex eligibility

All sexes

Study type

Observational

Primary location

Zhongshan Ophthalmic Center, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location status: Recruiting

Location contact

Sheng Liu

CONTACT

[email protected]

13622284795

Sheng Liu

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Abnormal group: Embryos with clinically confirmed embryonic developmental abnormalities requiring medical termination of pregnancy; intact retinal, visual and cognitive brain tissues available for snATAC-seq, scRNA-seq, electrophysiology, proteomics and RNAscope detection.

Normal group: Embryos confirmed free of any ocular and central nervous developmental defects by prenatal examination and anatomical observation; intact embryonic ocular and brain tissues meeting all experimental detection standards.

All sample donors have signed written informed consent authorizing the use of residual embryonic tissues for scientific research, with no monetary compensation involved.

Exclusion criteria

  • Embryonic ocular or brain tissues with severe necrosis, structural damage or microbial contamination that cannot support multi-omics and functional experiments.

Donors who withdraw or refuse the consent for tissue research use. Samples with irregular collection, transportation or cryopreservation procedures resulting in tissue degradation and failure to meet experimental requirements.

Treatment and study plan

Tissue collection and multi-omics sequencing analysis

Other

This observational study collects discarded human embryonic ocular and brain tissues from patients undergoing clinically indicated termination of pregnancy, with gestational age ranging from 9 to 40 weeks. We separate retinal, visual cortex and high-order cognitive cortex tissues, then perform single-cell multi-omics sequencing including transcriptome, chromatin accessibility and proteome profiling. The data is used to explore retinal neurogenesis, neuronal developmental trajectories and multi-modal cell atlas of embryonic visual system, without any clinical intervention on participants.

Primary outcomes

  1. Single-cell transcriptomic atlas and developmental trajectory of embryonic retinal and visual cortical neurons

    Time frame: Day 1 of tissue collection

    Perform single-cell RNA sequencing on human embryonic eye and brain tissues from abnormal developmental group and normal control group. Identify all cell subtypes in retina and visual-associated cognitive cortex, reconstruct continuous developmental trajectory of retinal neurogenesis and visual cortical neurons, and compare neuronal subtype distribution differences between the two groups.

  2. Genome-wide chromatin open regions in embryonic visual tissues

    Time frame: Day 1 of tissue collection

    Genome-wide chromatin open regions are detected via snATAC-seq on embryonic ocular and brain tissues from case and control groups.

  3. Differential chromatin accessibility between normal and malformed embryonic visual tissues

    Time frame: Day 1 of tissue collection

    Differential chromatin accessibility signals are identified via integrated analysis of snATAC-seq and scRNA-seq data from embryonic ocular and brain tissues.

  4. Candidate pathogenic genes underlying embryonic visual developmental abnormalities

    Time frame: Day 1 of tissue collection

    Genes linked to abnormal embryonic visual development are screened based on differential chromatin and transcriptomic profiles.

Secondary outcomes

  1. Action potential firing patterns of embryonic visual neurons

    Time frame: Day 1 of tissue collection

    Action potential firing patterns are recorded via combined Patch-seq and MEA on primary cultured retinal and visual cortical neurons from case and control embryonic tissues.

  2. Synchronous electrical activity of embryonic neuronal networks

    Time frame: Day 1 of tissue collection

    Neuronal network synchronous electrical activity is recorded via combined Patch-seq and MEA on primary cultured retinal and visual cortical neurons from case and control embryonic tissues.

  3. Spatial expression localization of key visual development genes detected by RNAscope

    Time frame: The day 1 of embryonic tissue collection after clinical termination of pregnancy

    RNAscope in situ hybridization is conducted on embryonic retinal and brain tissue slices to visualize the spatial distribution and quantitative expression levels of candidate pathogenic genes screened from multi-omics data. Compare the spatial gene expression differences between normal embryonic visual tissues and tissues with ocular developmental defects.

  4. Differentially expressed proteins identified via global proteome sequencing

    Time frame: Day 1 of tissue collection

    Global proteome sequencing is performed on embryonic ocular and brain tissues to generate lists of differentially expressed proteins linked to retinal neurogenesis and visual cortical development.

  5. Spatial localization and expression abundance of proteins via immunohistochemistry

    Time frame: Day 1 of tissue collection

    Immunohistochemistry staining is applied on embryonic tissue sections to detect spatial localization and expression abundance of core differentially expressed proteins.

Study contacts

Contact information is provided by the study sponsor or research team.

Jing Su

CONTACT

[email protected]

15999937669

Sheng Liu, Doctor

CONTACT

[email protected]

13622284795

Sponsors and collaborators

Lead sponsor

Sheng Liu

Other

Collaborators

  • Third Affiliated Hospital, Sun Yat-Sen University

Registry information

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Jul 7, 2026
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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