Sleeping Stem Cells Successfully Awakened: New Hope For Regenerating The Human Retina Damaged By Disease Or Injury

Scientists at Schepens Eye Research Institute have discovered what chemical in the eye triggers the dormant capacity of certain non-neuronal cells to transform into progenitor cells, a stem-like cell that can generate new retinal cells. The discovery, published in the March issue of Investigative Ophthalmology and Visual Science (IOVS), offers new hope to victims of diseases that harm the retina, such as macular degeneration and retinitis pigmentosa.

“This study is very significant. It means it might be possible to turn on the eye’s own resources to regenerate damaged retinas, without the need for transplanting outside retinal tissue or stem cells,” says Dr. Dong Feng Chen, associate scientist at Schepens Eye Research Institute and Harvard Medical School, and the principal investigator of the study. “If our next steps work in animal disease models, we believe that clinical testing could happen fairly quickly.”

Scientists have long been aware of M??ller cells (which exist in great abundance in the eye) and have generally assumed that they were responsible for keeping retinal tissue protected and clear of debris. In recent years, however, researchers have reported that these cells sometimes exhibit progenitor cell behavior and re-enter the cell cycle (dividing and differentiating into other type of cells). Progenitor cells are similar to stem cells but are more mature and are more limited in the number of cells types they can become.

But until this study, scientists have not understood what triggers the transformation. In their study, Chen and her team observed that when the naturally occurring chemicals known as glutamate and aminoadipate (which is a derivative of glutamate) were injected into the eye, the M??ller cells began to divide and proliferate. Not certain if these chemicals directly signaled the transformation, they tested them in the laboratory and in mice.

They added each chemical separately to cultures of pure M??ller cells and injected each into the space below the retina in healthy mice. In both cases, the cells became progenitor cells and then changed into retinal cells. And with aminoadipate, the newly minted retinal cells migrated to where they might be needed in the retina and turned into desirable cell types. Specifically, they showed that by injecting the chemical below the retina, the cells give rise to new photoreceptors – the type of cells that are lost in retinitis pigmentosa or macular degeneration, as a result, leading to blindness.

The team’s next step will be to test this process in animals that have been bred to have diseases that mimic macular degeneration and retinitis pigmentosa. The goal would be to learn if damaged retinas regenerate and vision improves. The team will likely use just aminoadipate because it only binds with M??ller cells without the side effects of glutamate, which can actually harm retina cells in large doses.

“We believe that a drug created from the chemical aminoadipate or a similar compound has great potential for healing damaged retinas,” says Chen.

Other authors of the study include:

Masumi Takeda 1,2,3
Akira Takamiya 1,2,3
Jian-wei Jiao 1,2
Kin-Sang Cho 1,2
Simon G. Trevino 1
Takahiko Matsuda 4
Dong F. Chen 1,2

1 The Schepens Eye Research Institute, Boston, Massachusetts

2 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts

3 Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan

4 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts.

Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the nation.

Source: Patti Jacobs

Schepens Eye Research Institute

Vigorous Exercise May Help Prevent Vision Loss

There’s another reason to dust off those running shoes. Vigorous exercise may help prevent vision loss, according to a pair of studies from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory. The studies tracked approximately 41,000 runners for more than seven years, and found that running reduced the risk of both cataracts and age-related macular degeneration.

The research, which is among the first to suggest that vigorous exercise may help prevent vision loss, offers hope for people seeking to fend off the onset of eye disease.

“In addition to obtaining regular eye exams, people can take a more active role in preserving their vision,” says Paul Williams, an epidemiologist in Berkeley Lab’s Life Sciences Division who conducted the research. “The studies suggest that people can perhaps lessen their risk for these diseases by taking part in a fitness regimen that includes vigorous exercise.”

A cataract, which is a cloudy opacity of the eye lens, is the leading cause of blindness. More than one-half of people in the U.S. over the age of 65 suffer from some form of cataracts. Age-related macular degeneration, which is damage to the retina, is the leading cause of irreversible vision loss in older white Americans, affecting 28 percent of people aged 75 and older.

The diseases have several known risk factors, such as sunlight exposure and diabetes in the case of cataracts, but few interventions. Now, it appears that vigorous cardiovascular exercise may be one way to derail the diseases.

To conduct the research, Williams analyzed data collected in the National Runners’ Health Study, which he established in 1991 to determine the health benefits of running.

In this case, he followed approximately 29,000 male runners and 12,000 female runners for more than seven years. Of these people, 733 men reported being diagnosed with cataracts on a questionnaire filled out at the end of the study. Too few women reported cataracts to track.

Men who ran more than 5.7 miles per day had a 35 percent lower risk of developing cataracts than men who ran less than 1.4 miles per day. The study also analyzed men’s 10-kilometer race performances, which is a good indicator of overall fitness. The fittest men boasted one-half the risk of developing cataracts compared to the least-fit men.

A second study found that running appeared to reduce the risk of age-related macular degeneration. In the study, 152 men and women reported being diagnosed with the disease. Compared to people who ran less than 1.2 miles per day, people who averaged between 1.2 and 2.4 miles per day had a 19 percent lower risk for the disease, and people who ran more than 2.4 miles per day had between 42 percent and 54 percent lower risk of the disease.

“These findings are compelling because of the large size of the study, and the fact that we are looking at something that is fairly well defined: vigorous exercise, as opposed to more moderate exercise,” says Williams.

Most of the runners in the study exceeded the current public health recommendations for physical activity, which is at least 30 minutes of moderate-intensity activities such as brisk walking five days a week, or smaller doses of more vigorous exercise such as running. It is unclear whether people might also lower their risk for cataracts and age-related macular degeneration by walking.

“We know there are important health benefits to walking, including lowering heart disease risk,” says Williams. “It is quite likely that the studies’ results might apply to a lesser extent to smaller doses of more moderate exercise.”

Williams also adds that further research is needed to explore why there is a link between vigorous exercise and a decreased risk for eye disease.

“We know some of the physiological benefits of exercise, and we know about the physiological background of these diseases, so we need to better understand where there’s an overlap,” says Williams.

The studies are published in the January 2009 issue of Investigative Ophthalmology and Visual Science. They were supported in part by grants from the National Heart Lung and Blood Institute.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at lbl.

More information on Williams’ research can be found at healthresearch.lbl.

Source: Dan Krotz

DOE/Lawrence Berkeley National Laboratory