Study details how genes in retina get regulated during development


A genome topology map of human retina development lays the foundation for understanding diverse clinical phenotypes in simple and complex eye diseases.

©Vlad Kochelaevskiy –

Image credit: ©Vlad Kochelaevskiy –

A team of researchers at the National Institutes of Health have mapped the 3D organization of genetic material of key developmental stages of human retinal formation, using intricate models of a retina grown in the lab.

According to an NIH/National Eye Institute news release, the findings lay a foundation for understanding clinical traits in many eye diseases, and reveal a highly dynamic process by which the architecture of chromatin, the DNA and proteins that form chromosomes, regulates gene expression.1 The findings were published in Cell Reports.2

Anand Swaroop, PhD, chief of the Neurobiology, Neurodegeneration, and Repair Laboratory at the National Eye Institute (NEI), part of NIH, served as the study’s lead investigator.

“These results provide insights into the heritable genetic landscape of the developing human retina, especially for the most abundant cell types that are commonly associated with vision impairment in retinal diseases,” Swaroop said in the NIH/NEI news release.

By utilizing deep Hi-C sequencing, a tool used for studying 3D genome organization, the researchers were able to create a high-resolution map of chromatin in a human retinal organoid at 5 key points in development. Organoids are tissue models grown in a lab and engineered to replicate the function and biology of a specific type of tissue in a living body.1

According to the NIH/NEI news release, genes, the sequences that code for RNA and proteins, are interspersed throughout long strands of DNA. Those DNA strands are placed into chromatin fibers, which are spooled around histone proteins and are looped multiple times to form highly compact structures that fit into the cell nucleus.

Moreover, the loops create millions of points where genes encounter non-coding DNA sequences, such as super enhancers, promoters, and silencers that regulate gene expression.1

These had long been considered “junk DNA,” and the non-coding sequences today are seen as playing a key role in controlling which genes get expressed in a cell and when. Researchers have examined chromatin’s 3D architecture to determine how these non-coding regulatory elements exert control even when their location on a DNA strand is remote from the genes they regulate.

At each of the 5 key developmental stages of retinal organoids, billions of chromatin contact point pairs were sequenced and analyzed.1

NIH/NEI noted in the news release the research team’s results uncovered an interesting image, with spatial organization of the genome within the nucleus is transformed during retinal development, facilitating expression of specific genes at key time periods. For example, at a stage when immature cells start developing retinal cell characteristics, chromatin contact points shift from a mostly proximal-enriched state to add more distal interactions.

According to the news release, the researchers also found that there seems to be a hierarchy of compartments that organize the contact point interactions. Some of these compartments, called “A” and “B”, are stable, but others swap during development, which further serves to enhance or inhibit gene expression.

“The datasets resulting from this research serve as a foundation for future investigations into how non-coding sections of the genome are relevant for understanding divergent phenotypes in single gene mutation (Mendelian) disorders, as well as complex retinal diseases,” Swaroop concluded.

According to the news release, the study was funded by the NEI Intramural Research Program (ZIAEY000450 and ZIAEY000546). NEI is part of the National Institutes of Health.

  1. NIH/National Eye Institute. News release. NIH study shows how genes in retina get regulated during development. Published December 13, 2023. Accessed December 14, 2023.
  2. Qu Z, Batz Z, Singh N, Marchal C, Swaroop A, Cell. Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids. Published December 2, 2023. Accessed December 14, 2023. DOI:
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