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Eye cells grown at Johns Hopkins may lead to a cure for some forms of blindness

Eye cells grown at Johns Hopkins may lead to a cure for some forms of blindness

Drs. Donald Zack and Valentin Sluch spent 30 anxious days waiting for their experiment to yield results.

They were eager to see if the retinal ganglion cells growing in their lab would turn red, indicating that they'd successfully edited the cells' DNA. Turning the eye cells red would allow them to be sorted from other cells and potentially provide the key to research that one day could lead to a cure for blindness caused by glaucoma or multiple sclerosis.

"I was checking every day," Sluch said. "When I first saw red cells in the cultures, I was really excited and I ran to get a colleague to tell them that it worked."

The breakthrough of growing eye cells in a lab, developed by Johns Hopkins University researchers, will also allow them to better understand the diseases and develop better drug therapies. Hopkins is already testing drug therapies through a five-year partnership with German pharmaceutical company Bayer that began earlier this year. Existing drug therapies work by reducing the pressure in the eye, which slows the progression of blindness.

The Hopkins researchers cautioned that there are many hurdles to overcome before they could develop a cure for blindness with transplanted optic nerves but said this offered hope.

"If you talk to patients and they rate what they're most scared of, obviously it's cancer and dying, but vision always comes out as one of the things that people are afraid of losing and really value," said Zack, a professor of ophthalmology at the Johns Hopkins School of Medicine who lead the study growing eye cells. "It would really change their lives."

Zack, who is also co-director of the Johns Hopkins Center for Stem Cells and Ocular Regenerative Medicine, developed the cells with Sluch, a former Johns Hopkins biochemistry, cellular and molecular biology student who is now a postdoctoral scholar at Novartis, a pharmaceutical company. Their research was published in November in the journal Scientific Reports.

The retinal ganglion cells the researchers grew are a type of cell found in the retina that has a long tail called an axon that becomes the optic nerve, which connects the eye to the brain. In diseases such as glaucoma and multiple sclerosis, the optic nerve becomes damaged, making it difficult or impossible for the eye to communicate with the brain.

The ganglion cells were grown from induced pluripotent stem cells, a type of stem cell made from the cells of an adult. The other type of stem cells, which come from human embryos, sometimes draw ethical or religious objections, Zack said.

The researchers edited the DNA of the cells to make them turn red so that a machine could separate them from other types of retinal cells, leaving them with a dish of pure retinal ganglion cells.

The researchers used a genome editing laboratory tool called CRISPR-Cas9 that was only developed a couple of years ago.

Zack is working with a bioengineer who placed the newly grown retinal cells on a form made of fibers that helped it grow in the shape of the optic nerve. Researchers elsewhere are taking note of the discovery and are working toward developing a way to transplant a new optic nerve or develop new drug therapies, he said.

Despite these advances, the researchers don't want to raise hopes that a cure for blindness is just around the corner. Zack said he was reluctant to estimate when such a transplant would be a reality. Even if a transplant became possible, any vision restored would likely be blurry and dim, Sluch said.

"Right now for a person that's completely blind, just being able to know what time of day it might be or if the lights are on in a room might be a big improvement in their life," Sluch said. "But I want to be realistic and say it'll take a lot of work to even get to that point."

More than 3 million Americans have glaucoma, according to the BrightFocus Foundation, a nonprofit supporting research into glaucoma and other diseases. Up to half of the 2.3 million people worldwide with multiple sclerosis, or MS, develop optic neuritis, a condition that can lead to partial or total blindness. MS affects nerve fibers and disrupts communication between the brain and the rest of the body.

Although diabetes can lead to blindness, Zack said some features of that disease may make a potential transplant more difficult.

Glaucoma patients lose their peripheral vision first. It is more common in older people and can take many years before blindness occurs.

If researchers were able to develop a way to grow a new optic nerve and transplant it in a patient, the patient might develop glaucoma again, but "it would reset the clock even if the damage was ongoing," said David Glasser, president of the Maryland Society of Eye Physicians and a part-time professor at Johns Hopkins.

"If we could restore their vision, that might give them another 10, 20, 30 years," Glasser said.

But it's unclear how the cells would hook up to the brain even if they were transplanted into the eye. Such issues are why stem-cell-grown organs aren't commonly used in transplants. "That's why we still use a liver from a donor and not one grown in the lab," Glasser said.

But those who work with glaucoma patients said that even slowing the progression of blindness would be a major step forward in the field.

"Unfortunately, with glaucoma at the moment we don't have a lot of great ways to slow down the progression of the disease," said Andrew Iwach, chairman of the board of the Glaucoma Research Foundation and executive director of the Glaucoma Center of San Francisco. "We're not there yet but we're making progress. Twenty-five years ago I had hope but I didn't see a pathway [to a cure], and now I see the possibility, which is really exciting."

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