Researchers map the genetics of the cell types of the mouse iris using genetic mapping

Johns Hopkins Medicine researchers report they have genetically mapped cells that make up the mouse’s iris, the thin, colored tissue that human eyes their distinct shades. The research uncovers four new types of cells within the iris, and maps the genetic changes that occur as the iris expands, as well as information about how the beginning stages of development affect the formation of the iris.

Researchers believe that the report may help scientists to connect the genetic similarities between eye of the mouse and the human eye. It could also provide clues for new diagnostic tests and treatments for diseases affecting the iris, such as anterior uveitis (an inflammatory condition) and congenital diseases where a part or all of the iris is missing.

Eyes are the most prominent feature of the human face, and we are prone to fixate on the eyes when we speak to one another. The iris has a prominent location, which makes it an easy access point to diagnose or treat medical conditions, but we need to understand it better.”

Jeremy Nathans, M.D., Ph.D., professor of genetics and molecular biology, Johns Hopkins University School of Medicine

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

A genetic sequencing technique, called single cell RNA sequencing, allowed researchers to begin deciphering the iris at a cell level by analyzing which genes were activated in the cell at a certain time. This enabled the researchers to map out closely related cell types, determined by the activity of their genes.

The method identified new distinctions, such as two types of iris structural cells known as 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 a drastic physical change, the researchers assert.

“The tissue is then arranged in an accordion-like pattern, so we wanted to know if the expression of genes was a result of the dramatic physical changes,” says Nathans.

Researchers utilized single cell RNA sequencing in order to examine relaxed, dilated and constricted retinas of mice. They found that , although there was no significant differences in the expression of genes in the two eyes, there were a number of dramatic differences in the way genes were expressed in the dilated eye, which is the stage where the iris tissue becomes the most compressed.

The researchers found that gene expression changes were the most evident in the dilator muscle cells, which includes EGR1 the gene that is responsible for responding to changes within the environment.

“This could suggest that the physical changes are stressful for the cells and they’re trying to adapt,” said Amir Rattner (Ph.D.), research associate in the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine.

The team also studied the iris’s development sources. cell lines.

Using mouse embryos that were genetically engineered to have glowing cells from the developing nervous system, referred to as the neural crest, researchers were able to follow the origins of iris cells.

“The majority of the iris cells derived 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 research could result in regenerative medicine or treatments using gene therapy to treat disorders in the eye.

The research was aided by the Howard Hughes Medical Institute.

Journal reference:

Wang, J., and. (2021) A transcriptome atlas of the iris of the mouse at single-cell resolution identifies cell types and the response of the genome to pupil dilation. eLife.

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Gemma Wilson

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