Resveratrol - found in red wine, grapes, blueberries, peanuts and other plants - stops out of control blood vessel growth in the eye, according to vision researchers at Washington University School of Medicine in St. Louis.

Rajendra S. Apte MD,PhD

The discovery has implications for preserving vision in blinding eye diseases such as diabetic retinopathy and age related macular degeneration, the leading cause of blindness in Americans over 50.

The formation of new blood vessels, called angiogenesis, also plays a key role in certain cancers and in atherosclerosis. Conducting experiments in mouse retinas, the researchers found that resveratrol can inhibit angiogenesis. Another surprise was the pathway through which resveratrol blocked angiogenesis. The findings are reported in the July issue of the American Journal of Pathology.

“A great deal of research has identified resveratrol as an anti aging compound, and given our interest in age related eye disease, we wanted to find out whether there was a link,” says Washington University retina specialist Rajendra S. Apte, MD, PhD, the study’s senior investigator. “There were reports on resveratrol’s effects on blood vessels in other parts of the body, but there was no evidence that it had any effects within the eye.”

The investigators studied mice that develop abnormal blood vessels in the retina after laser treatment. Apte’s team found that when the mice were given resveratrol, the abnormal blood vessels began to disappear.

Examining the blood-vessel cells in the laboratory, they identified a pathway - known as a eukaryotic elongation factor 2 kinase (eEF2) regulated pathway - that was responsible for the compound’s protective effects. That was a surprise because past research involving resveratrol’s anti aging effects had implicated a different mechanism that these experiments showed not to be involved.

“We have identified a novel pathway that could become a new target for therapies,” Apte says. “And we believe the pathway may be involved both in age related eye disease and in other diseases where angiogenesis plays a destructive role.”

Previous research into resveratrol’s influence on aging and obesity had identified interactions between the red wine compound and a group of proteins called sirtuins. Those proteins were not related to resveratrol’s effects on abnormal blood vessel formation. Instead, the researchers say that in addition to investigating resveratrol as a potential therapy, they also want to look more closely at the eEF2 pathway to determine whether it might provide a new set of targets for therapies, both for eye disease and other problems related to abnormal angiogenesis.

Apte, an assistant professor of ophthalmology and visual sciences and of developmental biology, says because resveratrol is given orally, patients may prefer it to many current treatments for retinal disease, which involve eye injections. The compound also is easily absorbed in the body.

In mice, resveratrol was effective both at preventing new blood vessels and at eliminating abnormal blood vessels that already had begun to develop.

“This could potentially be a preventive therapy in high risk patients,” he says. “And because it worked on existing, abnormal blood vessels in the animals, it may be a therapy that can be started after angiogenesis already is causing damage.”

Apte stresses that the mouse model of macular degeneration they used is not identical to the disease in human eyes. In addition, the mice received large resveratrol doses, much more than would be found in several bottles of red wine. If resveratrol therapy is tried in people with eye disease, it would need to be given in pill form because of the high doses required, Apte says.

There are three major eye diseases that resveratrol treatment may help: age related macular degeneration, diabetic retinopathy and retinopathy of prematurity. Age related macular degeneration involves the development of abnormal blood vessels beneath the center of the retina. It accounts for more than 40 percent of blindness among the elderly in nursing homes, and as baby boomers get older, the problem is expected to grow, with at least 8 million cases predicted by the year 2020.

In diabetic retinopathy, those blood vessels don’t develop beneath the retina. They grow into the retina itself. Diabetic retinopathy causes vision loss in about 20 percent of patients with diabetes. Almost 24 million people have diabetes in the United States alone.

Retinopathy of prematurity occurs when premature babies with immature retinas experience an obstruction in blood flow into the retina. In response, those children often develop abnormal blood vessels that can cause retinal detachment and interfere with vision. Worldwide, that condition blinds 50,000 newborn babies each year.

Apte says the pathway his laboratory has identified may be active not only in those blinding eye diseases, but in cancers and atherosclerosis as well. If so, then one day it might be possible to use resveratrol to improve eyesight and to prevent cardiovascular disease and some types of cancer, too.

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KINGSTON, R.I.

URI pharmacy researcher finds beneficial compounds in pure maple syrup
Most are disease fighting anti-oxidants

Before you dig in to your next stack of French toast or waffles, you might want to pour on pure maple syrup.

That’s because University of Rhode Island researcher Navindra Seeram, who specializes in medicinal plant research, has found more than 20 compounds in maple syrup from Canada that have been linked to human health, 13 of which are newly discovered in maple syrup. In addition, eight of the compounds have been found in the Acer (maple) family for the first time.

The URI assistant professor of biomedical and pharmaceutical sciences in URI’s College of Pharmacy presented his findings Sunday, March 21 at the American Chemical Society’s Annual Meeting in San Francisco. The project was made possible by Conseil pour le développement de l’agriculture du Québec (CDAQ), with funding provided by Agriculture and Agri-Food Canada’s Advancing Canadian Agriculture and Agri-Food (ACAAF) program.

Several of these anti-oxidant compounds newly identified in maple syrup are also reported to have anti-cancer, anti-bacterial and anti-diabetic properties.

Prior to the study, the Federation of Quebec Maple Syrup Producers already knew that its product was full of naturally occurring minerals such as zinc, thiamine and calcium. But it enlisted Seeram to research the presence of plant anti-oxidants. The Federation awarded Seeram a two-year, $115,000 grant with the help of the CDAQ and Agriculture and Agri-Food Canada. His research continues to determine if the compounds exist in beneficial quantities.

Serge Beaulieu, president of the Federation of Quebec Maple Syrup Producers, said Seeram’s lab is but one in an expanding multi-national network of research facilities dedicated to the study of maple products from Canada.

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Famous for its antioxidant properties and role in tissue repair, vitamin C is touted as beneficial for illnesses ranging from the common cold to cancer and perhaps even for slowing the aging process. Now, a study published online on December 24th by Cell Press in the journal Cell Stem Cell uncovers an unexpected new role for this natural compound: facilitating the generation of embryonic like stem cells from adult cells. Over the past few years, we have learned that adult cells can be reprogrammed into cells with characteristics similar to embryonic stem cells by turning on a select set of genes. Although the reprogrammed cells, called induced pluripotent stem cells (iPSCs), have tremendous potential for regenerative medicine, the conversion is extremely inefficient.

“The low efficiency of the reprogramming process has hampered progress with this technology and is indicative of how little we understand it. Further, this process is most challenging in human cells, raising a significant barrier for producing iPSCs and serious concerns about the quality of the cells that are generated,” explains senior study author Dr. Duanqing Pei from the South China Institute for Stem Cell Biology and Regenerative Medicine at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences.

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Scientists in Sweden are reporting for the first time that a group of drugs used to treat heart failure shows promise for fighting colon cancer. The study is in ACS’ Journal of Natural Products, a monthly publication. Colon cancer is the third most common cancer in the United States, with more than 150,000 cases diagnosed in the U.S. each year.

The leaves of the oriental foxglove plant contain digitoxin, a drug used to treat heart disease. It is in a family of medications that now show promise for fighting colon cancer photo: Wikimedia Commons

Jenny Felth, Joachim Gullbo, and colleagues note that cardiac glycosides are a family of naturally derived drugs used to treat congestive heart failure and abnormal heart rhythms. Scientists have suspected for some time, based on previous research, that these heart drugs may have promise for fighting many different types of cancer. Despite this, knowledge on effects in colon cancer or combination effects with other anti cancer drugs is lacking. But scientists know little about their potential anticancer effects and have not tested these substances against colon cancer.

As part of a larger study to screen and identify natural substances with activity against colon cancer, the scientists picked several cardiac glycosides for further study. They tested five of these heart drugs against laboratory cultures of human colon cancer cells and found that they were all effective, to varying degrees, at killing the cancer cells. The sensitivity, however, was rather low when compared to that of other cancer cell types reported previously. Several of the drugs also showed increased anticancer activity when combined with certain drugs used for standard chemotherapy. The findings suggest that these heart drugs may affect colon cancer outcome when used alone or in combination with conventional chemotherapy drugs, they say.

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HOUSTON - Green tea extract has shown promise as cancer prevention agent for oral cancer in patients with a premalignant condition known as oral leukoplakia, according to researchers at The University of Texas M. D. Anderson Cancer Center. The study, published online in Cancer Prevention Research, is the first to examine green tea as a chemopreventative agent in this high risk patient population. The researchers found that more than half of the oral leukoplakia patients who took the extract had a clinical response.

Long investigated in laboratory, epidemiological and clinical settings for several cancer types, green tea is rich in polyphenols, which have been known to inhibit carcinogenesis in preclinical models. Still, clinical results have been mixed.

“While still very early, and not definitive proof that green tea is an effective preventive agent, these results certainly encourage more study for patients at highest risk for oral cancer,” said Vassiliki Papadimitrakopoulou, M.D., professor in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology, and the study’s senior author. “The extract’s lack of toxicity is attractive - in prevention trials, it’s very important to remember that these are otherwise healthy individuals and we need to ensure that agents studied produce no harm.”

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