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Cell Types of the Iris Mapped in Mice

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Johns Hopkins Medicine researchers report they have genetically mapped the cell types that make up the mouse iris — the thin disc of pigmented tissue that, in humans, gives eyes their distinct colors. The research reveals four new cell types in the iris, maps the genetic changes that occur when the iris dilates, and provides information about how the iris forms during early development.

The report, say the researchers, may help scientists connect genetic similarities between the mouse and human eye, and offer clues to develop new diagnostic tests and treatments for diseases that affect the iris — such as anterior uveitis, an inflammatory condition — and congenital diseases in which all or part of the iris is missing.

“Eyes are a defining characteristic of the human face, and we tend to focus on the eyes when speaking to one another, ,” says Jeremy Nathans, M.D., Ph.D., professor of molecular biology and genetics at the Johns Hopkins University School of Medicine. “The iris has a prominent place, making it an easy access point to diagnose or treat medical conditions, but we need to understand it better.”

A summary of the research was published Nov. 16 in eLife.

A genetic sequencing technology, called single cell RNA sequencing, allowed the researchers to begin deciphering the iris at a cellular level by analyzing which genes were turned on in a cell at a given time. This enabled the researchers to chart out closely related cell types, determined by the activity of their genes.

The technique revealed new distinctions, including two types of iris structural cells called stroma and two types of smooth muscle cells that allow the iris to constrict in response to light.

When the iris constricts or dilates, it’s an extreme physical change, the researchers say.

“The tissue ends up in an accordion pattern, so we wondered whether a change in gene expression came along with the drastic physical changes,” says Nathans.

Using single cell RNA sequencing again to compare relaxed, dilated and constricted mouse iris tissues, the researchers found that while there was not much change in gene expression between a relaxed mouse eye and a constricted one, there were dramatic differences in the genes expressed in the dilated mouse eye — the stage where the iris tissue is most compressed.

Specifically, the researchers found the most gene expression change in dilator muscle cells, including a gene called EGR1, which is responsible for responding to changes in the environment across the body.

“This could be a signal that the physical changes are stressful to the cells and they are trying to adapt,” says Amir Rattner, Ph.D., research associate in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine.

Finally, the research team tracked the developmental origins of iris cells.

Using mouse embryos genetically engineered with glowing cells in the developing nervous system, called the neural crest, the researchers were able to follow where iris cells originated.

“The majority of the iris cells came from the neural crest, which gives us a fundamental understanding of how the iris develops,” says Jie Wang, Ph.D., postdoctoral fellow in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine.

The information could someday lead to regenerative medicine or gene therapy treatments for disorders in the eye.

Reference: Wang J, Rattner A, Nathans J. A transcriptome atlas of the mouse iris at single-cell resolution defines cell types and the genomic response to pupil dilation. eLife. 2021;10:e73477. doi: 10.7554/eLife.73477

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