Health News and Research
Resveratrol Potentially Reverses Diabetic Retinopathy and Wet ARMD
A new study reported in the July 2010 issue of the American Journal of Pathology demonstrates that resveratrol may help prevent and reverse certain eye diseases.
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, wrote the researchers at Washington University in St. Louis in their press release.
The process of angiogensis occurs when the body forms new blood vessels to help with healing and cell reproduction. But angiogenesis can spiral out of control and cause “pathologic angiogenesis” such as in the progression of cancer and the onset of heart disease or eye diseases.
“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.”
Pathologic angiogenesis in the eye leads to blindness, affecting either the back of the eye called the retina (resulting in diabetic retinopathy in the elderly or even blindness in infants) or the part of the eye called the macula that leads to age-related macular degeneration, which causes vision loss in more than 200,000 people every year and is the leading cause of irreversible visual impairment in the world.
As a result, finding ways to control angiogenesis is of primary importance. A new study in mice has found that resveratrol, a trace ingredient in grapes, may help with blood vessel health.
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. In this study, researchers found that resveratrol (given doses of 45 mg per kg of bodyweight for 7 days, equivalent to 3,000 mg/day for a 150 pound human) was able to stop angiogenesis in the eyes of 15 mice that were simulated to be characteristic of eye damage seen during diabetic retinopathy. The induced eye damage was performed on day 8 of the study. Using a pathway independent of the known sirtuin pathway, resveratrol was able to completely reverse the accelerated growth of blood vessels in the eye.
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
Abnormal angiogenesis is central to the pathophysiology of
diverse disease processes including cancers, ischemic and
atherosclerotic heart disease, and visually debilitating eye
disease. Resveratrol is a naturally occurring phytoalexin that
has been demonstrated to ameliorate and decelerate the aging
process as well as blunt end organ damage from obesity. These
effects of resveratrol are largely mediated by members of the
sirtuin family of proteins. We demonstrate that resveratrol can
inhibit pathological angiogenesis in vivo and in vitro by a
sirtuin-independent pathway. Resveratrol inhibits the
proliferation and migration of vascular endothelial cells by
activating eukaryotic elongation factor-2 kinase. The active
kinase in turn phosphorylates and inactivates elongation
factor-2, a key mediator of ribosomal transfer and protein
translation. Functional inhibition of the kinase by gene
deletion in vivo or RNA as well as pharmacological inhibition in
vitro is able to completely reverse the effects of resveratrol
on blood vessel growth. These studies have identified a novel
and critical pathway that promotes aberrant vascular
proliferation and one that is amenable to modulation by
pharmacological means. In addition, these results have uncovered
a sirtuin-independent pathway by which resveratrol regulates
Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS. Resveratrol Regulates Pathologic Angiogenesis by a Eukaryotic Elongation Factor-2 Kinase-Regulated Pathway. American Journal Of Pathology, 2010; DOI: 10.2353/ajpath.2010.090836
Key concepts: Resveratrol, ARMD, diabetic retinopathy