Scientists grow retinal nerve cells which could help people blinded by glaucoma, MS

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Scientists have developed a new method to efficiently turn human stem cells into retinal nerve cells that transmit visual signals from the eye to the brain, an advance that could lead to treatments for people blinded by glaucoma and multiple sclerosis (MS).

Death and dysfunction of these cells, known as retinal ganglion cells, cause vision loss in conditions like glaucoma and MS. "Our work could lead not only to a better understanding of the biology of the optic nerve, but also to a cell-based human model that could be used to discover drugs that stop or treat blinding conditions," said study leader Donald Zack, from the Johns Hopkins University School of Medicine in US. "And, eventually it could lead to the development of cell transplant therapies that restore vision in patients with glaucoma and MS," said Zack.

The laboratory process entails genetically modifying a line of human embryonic stem cells to become fluorescent upon their differentiation to retinal ganglion cells, and then using that cell line for development of new differentiation methods and characterisation of the resulting cells. Using a genome editing laboratory tool called CRISPR-Cas9, the researchers inserted a fluorescent protein gene into the stem cells' DNA.

This red fluorescent protein POU4F2 would be expressed only if another gene named BRN3B was also expressed. BRN3B is expressed by mature retinal ganglion cells, so once a cell differentiated into a retinal ganglion cell, it would appear red under a microscope.

Next, they used a technique called fluorescence-activated cell sorting to separate out the newly differentiated retinal ganglion cells from a mixture of different cells into a highly purified cell population. The cells showed biological and physical properties seen in retinal ganglion cells produced naturally, said Zack. Researchers also found that adding a naturally occurring plant chemical called forskolin on the first day of the process helped improve the cells' efficiency of becoming retinal ganglion cells. 
"By the 30th day of culture, there were obvious clumps of fluorescent cells visible under the microscope," said lead author Valentin Sluch, a former Johns Hopkins student. "It seems we can now isolate the cells and study them in a pure culture, which is something that wasn't possible before," Sluch said. "We hope that these cells can eventually lead to new treatments for glaucoma and other forms of optic nerve disease," said Zack.

The study was published in the journal Scientific Reports.