Tag: Macular degeneration

Macular Degeneration risk reduced 60% by eating Oranges

Macular Degeneration risk reduced 60% by eating Oranges

The research showed that people who ate at least one serving of oranges every day had more than a 60% reduced risk of developing late macular degeneration 15 years later.

Bamini Gopinath Gerald Liew Annette Kifley Victoria M Flood Nichole Joachim Joshua R Lewis Jonathan M Hodgson Paul Mitchell. Dietary flavonoids and the prevalence and 15-y incidence of age-related macular degeneration. American Journal of Clinical Nutrition, 2018 DOI: 10.1093/ajcn/nqy114

Aflibercept in AMD: no proof of added benefit

Manufacturer’s dossier did not contain any usable data for the comparison with ranibizumab

The drug aflibercept (trade name: Eylea) has been approved in Germany since November 2012 for the treatment of wet age-related macular degeneration (AMD). In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG) the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the current standard therapy. Such an added benefit cannot be derived from the dossier, however, as the manufacturer did not submit any suitable data for this comparison.

Patients in control group did not receive approval-compliant treatment

The Federal Joint Committee (G-BA) specified the drug ranibizumab as appropriate comparator therapy. In its dossier the pharmaceutical company cited two approval studies of aflibercept that directly compared aflibercept with ranibizumab. But in these studies, ranibizumab was not used according to its approval status. For instance, the continuation or discontinuation of treatment was not made dependent on whether the patients had achieved stable visual acuity or not. Although the manufacturer cited other documents in its dossier, these cannot be used for the benefit assessment, as they do not allow any reliable conclusions to be drawn on the comparison of aflibercept and ranibizumab. Overall, no added benefit of aflibercept can be derived from the data presented in the dossier.

G-BA decides on the extent of added benefit

The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer’s dossier and IQWiG‘s assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

An overview of the results of IQWiG‘s benefit assessment is given by a German-language executive summary. In addition, the website gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on aflibercept.

The G-BA website contains both general English-language information on benefit assessment pursuant to §35a Social Code Book V and specific German-language information on the assessment of aflibercept.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on www.informedhealthonline.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.

Study suggests link between regular aspirin use, increased risk of age-related macular degeneration: 3.7% vs 9.3%

Contact: Jie Jin Wang, Ph.D. jiejin.wang@sydney.edu.au JAMA and Archives Journals

CHICAGO – Regular aspirin use appears to be associated with an increased risk of neovascular age-related macular degeneration (AMD), which is a leading cause of blindness in older people, and it appears to be independent of a history of cardiovascular disease and smoking, according to a report published Online First by JAMA Internal Medicine, a JAMA Network publication.

Aspirin is one of the most widely used medications in the world and is commonly used in the prevention of cardiovascular disease, such as myocardial infarction (heart attack) and ischemic stroke. While a recent study suggested that regular aspirin use was associated with AMD, particularly the more visually devastating neovascular (wet) form, other studies have reported inconsistent findings. Smoking is also a preventable risk factor for AMD, the authors write in the study background.

Gerald Liew, Ph.D., of the University of Sydney, Australia, and colleagues examined whether regular aspirin use (defined as once or more per week in the past year) was associated with a higher risk of developing AMD by conducting a prospective analysis of data from an Australian study that included four examinations during a 15-year period. Of 2,389 participants, 257 individuals (10.8 percent) were regular aspirin users.

After the 15-year follow-up, 63 individuals (24.5 percent) developed incident neovascular AMD, according to the results.

“The cumulative incidence of neovascular AMD among nonregular aspirin users was 0.8 percent at five years, 1.6 percent at 10 years, and 3.7 percent at 15 years; among regular aspirin users, the cumulative incidence was 1.9 percent at five years, 7 percent at 10 years and 9.3 percent at 15 years, respectively,” the authors note. “Regular aspirin use was significantly associated with an increased incidence of neovascular AMD.”

The authors note that any decision concerning whether to stop aspirin therapy is “complex and needs to be individualized.”

“Currently, there is insufficient evidence to recommend changing clinical practice, except perhaps in patients with strong risk factors for neovascular AMD (e.g., existing late AMD in the fellow eye) in whom it may be appropriate to raise the potentially small risk of incident neovascular AMD with long-term aspirin therapy,” the authors conclude.

(JAMA Intern Med. Published online January 21, 2013. doi:10.1001/jamainternmed.2013.1583.)

Editor’s Note: This study was supported by project grants from the National Health & Medical Research Council Australia. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Relationship of Aspirin Use with Age-Related Macular Degeneration

In an invited commentary, Sanjay Kaul, M.D., and George A. Diamond, M.D., of Cedars-Sinai Medical Center, Los Angeles, write: “This study has important strengths and limitations. It provides evidence from the largest prospective cohort with more than five years of longitudinal evaluation reported to date using objective and standardized ascertainment of AMD.”

“The key limitation is the nonrandomized design of the study with its potential for residual (unmeasured or unobserved) confounding that cannot be mitigated by multivariate logistic regression or propensity score analysis,” the authors continue.

“From a purely science-of-medicine perspective, the strength of evidence is not sufficiently robust to be clinically directive. These findings are, at best, hypothesis-generating that should await validation in prospective randomized studies before guiding clinical practice or patient behavior,” the authors conclude. “However, from an art-of-medicine perspective, based on the limited amount of available evidence, there are some courses of action available to the thoughtful clinician. In the absence of definitive evidence regarding whether limiting aspirin exposure mitigates AMD risk, one obvious course of action is to maintain the status quo.”

(JAMA Intern Med. Published online January 21, 2013. doi:10.1001/jamainternmed.2013.2530.)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

###

To contact Jie Jin Wang, Ph.D., email jiejin.wang@sydney.edu.au. To contact commentary author Sanjay Kaul, M.D., email sanjay.kaul@cshs.org.

145th Health Research Report 28 DEC 2012

 

Editors Top Five:

Null…Only like have 5 articles.

In this issue:

  1. Regular aspirin use 10 or more years ago associated with increased risk of type of age-related macular degeneration
  2. JAMA article discusses critical need for iodine supplements during pregnancy and while nursing
  3. Impaired melatonin secretion may play a role in premenstrual syndrome
  4. Are GMOs “sterilizing” Serbia?
  5. Maybe it’s time for a little human enhancement – Morally enhancing drugs added to our Water Supply

Regular aspirin use 10 or more years ago associated with increased risk of type of age-related macular degeneration

CHICAGO ‑ Among nearly 5,000 study participants, regular aspirin use reported ten years prior was associated with a small but statistically significant increase in the risk of neovascular age‑related macular degeneration, according to a study in the December 19 issue of JAMA.

“Aspirin use in the United States is widespread, with an estimated 19.3 percent of adults reporting regular consumption, and reported use increases with age,” according to background information in the study. “The results of cross-sectional studies of aspirin use and its relation to age-related macular degeneration (AMD) have been inconsistent. AMD is a potentially blinding condition for which prevalence and incidence are increasing with the increased survival of the population, and regular use of aspirin is common and becoming more widespread in persons in the age range at highest risk for this disease. Therefore, it is imperative to further examine this potential association.”

Barbara E. K. Klein, M.D., M.P.H., of the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues conducted a study to examine the association between aspirin use and AMD. The researchers used data from the Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (n = 4,926) were 43 to 86 years of age at entry in the study. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. The average duration of follow-up was 14.8 years.

For the study, the researchers measured the incidences of different types of AMD (early, late, and 2 subtypes of late AMD [neovascular AMD and pure geographic atrophy]).

There were 512 incident cases of early AMD and 117 incident cases of late AMD over the course of the study. The researchers found that regular use of aspirin use 10 years prior to the retinal examination was associated with late AMD (age- and sex-adjusted incidence, 1.8 percent for users vs. 1.0 percent for nonusers). When examining the relationships by late AMD subtype, neovascular AMD was significantly associated with such use (age-and sex-adjusted incidence, 1.4 percent for users vs. 0.6 percent for nonusers), but not for pure geographic atrophy. Aspirin use 5 years or 10 years prior to retinal examination was not associated with incident early AMD.

“Our findings are consistent with a small but statistically significant association between regular aspirin use and incidence of neovascular AMD. Additional replication is required to confirm our observations. If confirmed, defining the causal mechanisms may be important in developing methods to block this effect to prevent or retard the development of neovascular AMD in persons who use aspirin, especially to prevent CVD,” the authors conclude.

JAMA article discusses critical need for iodine supplements during pregnancy and while nursing

(Boston/Washington) – A viewpoint in this week’s Journal of the American Medical Association (JAMA) discusses the issue of iodine deficiency in pregnant women in the U.S. and the potential negative health implications for both mothers and their children from this deficiency.

Alex Stagnaro-Green, MD, MHPE, professor of medicine and professor of obstetrics and gynecology at the George Washington University (GW) School of Medicine and Health Sciences (SMHS), is the paper’s lead author. Elizabeth Pearce, MD, MSc, associate professor of medicine at Boston University School of Medicine (BUSM), serves as co-author on the paper. The authors hope to start a conversation in the healthcare community on how to better protect the health of mothers and their children.

“Iodine levels in the US have been decreasing, which has the potential to negatively impact the mother and unborn child,” said Stagnaro-Green. “It’s time for all healthcare professionals to make sure that every pregnant and breast-feeding woman gets supplemental iodine during pregnancy and while they are breast-feeding.”

Iodine, which is not naturally made in the human body, must be consumed through foods rich in the element or through supplements. Iodine is required for the production of thyroid hormone, and adequate thyroid hormone levels are critical for normal fetal neurodevelopment. National and international health organizations currently recommend that pregnant women take at least 150 µg of potassium iodide daily.

“There is concern that even mild iodine deficiency in pregnant women could lead to children with lower IQ’s,” said Pearce. Iodine deficiency remains the leading cause of preventable mental retardation worldwide. Other risks of iodine deficiency include maternal and fetal goiter and increased pregnancy loss and infant mortality.

Guidelines from the American Thyroid Association, Endocrine Society and Teratology Society have recommended daily iodine supplements for women in the U.S. who are pregnant, lactating or planning a pregnancy. However, these recommendations have not been widely adopted and many prenatal multivitamins sold do not contain iodine. Previous studies have shown that approximately only 20 percent of women in the U.S. take supplements with iodine.

“It is imperative that collaborations develop among health care providers and the pharmaceutical industry to ensure that all prenatal vitamins contain at least 150 µg of iodine,” said Pearce.

Dr. Stagnaro-Green recommends that, “every prenatal vitamin in the US should have iodine supplementation.”

Impaired melatonin secretion may play a role in premenstrual syndrome

A new study by Douglas Mental Health University Institute researchers shows altered body rhythms of the hormone melatonin in Premenstrual dysphoric disorder (PMDD) women with insomnia. This finding may help explain some of the sleep disruptions experienced by women with PMDD, also known as premenstrual syndrome. PMDD is a mood disorder which appears in the week preceding menses, and affects about 3-8% of women. PMDD sufferers can experience depression, tension, and irritability of sufficient intensity to interfere with daily activities and relationships. Disturbed sleep is also a common symptom of the disorder, with up to 70% of patients frequently reporting either poor sleep quality with increased awakenings or excessive sleepiness during the symptomatic phase.

First study in a highly controlled time-isolation environment

Dr. Diane B. Boivin’s team at the Centre for Study and Treatment of Circadian Rhythms at the Douglas Institute investigated how rhythms of the hormone melatonin vary across the 24-hour day in a group of women with PMDD and a group of healthy controls. In the study, participants underwent two 24-hour laboratory visits, once during the pre-ovulatory follicular phase and again during the post-ovulatory luteal phase of the menstrual cycle. Each visit consisted of intensive physiological monitoring under highly controlled time-isolation conditions. During this time, blood samples were collected to determine circulating plasma melatonin levels.

The main finding was that compared to healthy controls, PMDD women had significantly decreased melatonin secretion levels during the night-time hours. PMDD women also had a further reduction of melatonin levels during their symptomatic luteal phase compared to the asymptomatic follicular phase.

Clinical implications of reduced melatonin in PMDD The prevalence of insomnia and depression are both about twice as high in women than in men, yet the reasons for this are still not fully understood. The current results highlight the importance of considering melatonin and circadian rhythms as factors leading to PMDD, with many clinical implications.

“Clearly understanding the mechanisms and specific pathophysiology of PMDD can help improve treatments, including both pharmacologic and non-pharmacologic approaches, for this disorder”, said lead author Dr. Ari Shechter.

By targeting the melatonin system specifically, or, more broadly, the circadian system, clinicians may be able to better treat symptoms, including insomnia, in PMDD.

ARE GMOS “STERILIZING” SERBIA?

Timur Blokhin

Dec 27, 2012 15:52

It’s no time for joking in Serbia: the ban on GMOs currently in force could spoil the country’s relations with the United States, and close the doors of the WTO for Belgrade. A statement to this effect was made the other day by representative of the American Embassy in Serbia Victoria Nibarger.

Serbian defenders of healthy eating cannot but curse at the already passed stages on the way to the WTO and the adoption of the Codex Alimentarius. This is a set of food standards, which implies, in particular, high levels of growth hormones in meat. Ecologists cite the case of an eight-year-old girl from Belgrade who is experiencing premature puberty and intensive hair growth because of these hormones taken with food. Some experts assert that when such “precocious” children come of age, they face a risk of breast or prostate cancer, depending on their gender.

Anti-transgenic sentiments are strong in Serbia. They impose GMO on us in order to sterilize our nation, Executive Director of the Novi Sada Ecological Movement Nikola Aleksich says in an interview with the Voice of Russia:

“Serbia is experiencing serious problems because of the illegal import of GMOs. 350 thousand married couples cannot conceive a child. And as for the increasing number of cases of cancer in Serbia, nobody dares to speak about it, these data are secret.”

For the past two decades scientists around the world have been arguing about the dangers of GMOs, and Russia is no exception. Doctor of Biological Sciences and international expert on environmental and food security Irina Ermakova believes that very inefficient technologies are used when GMOs are being created, that’s why such products cannot be safe by definition:

“During my experiments I added genetically-modified soya to the food of female rats. I was interested in what would happen to their progenies. More than 50% of young rats died in the first two-three weeks, about one half of the remaining rats were physically underdeveloped and they were not procreant. Later these studies were repeated with mice and hamsters in other Russian institutes and the results were the same: infertility. Many similar studies, independent of transnational corporations, are being carried out in the world, and they all show negative results. This means the deterioration of internal organs and cancer. Foreign colleagues have brought attention to the fact that companies often test the impact of GMOs during the first two-three months, but huge tumors appear during the 4th – 5th month.”

GMOs are accompanied by a trade war, and during the war the end justifies the means, including juggling facts and half-truths, Vadim Lebedev says.

In fact, this is not only an ecological issue, but also an economic one as well. It is indicative that one of the main lobbyists of GMOs in Serbia is the MK Grupa Company, which is a representative of the Monsanto Corporation, the main supplier of GMO seeds in the world. Executive Director of Novi Sada Ecological Movement Nikola Aleksich believes that if Serbia gives the go-ahead to transgenic seeds, it will find itself in economic slavery:

“We have several producers of seeds, which are widely known, including in Russia. If the country allows the GMO seeds, these institutions will close, five thousand people will lose their jobs, and Serbia will become dependent on the products of the Monsanto Corporation. And the purchase of their products will cost a minimum of 180 million euros per year. Thousands of farmers in India have committed suicide because the activities of Monsanto literally led them in a debtor’s prison. In addition, Europe and the whole world are interested in organic agricultural products, which Serbia can supply. Thus, after adopting GMOs, we will lose a promising market.”

It is well known that removing the ban on GMOs is one of the conditions of accession to the World Trade Organization. Belgrade is used to endless “must” and “should”: in Serbia, they even joke that the end of the world did not come because the country did not fulfill the preconditions of the Apocalypse. However, the “chain” is much longer, because membership in the WTO, in its turn, is the necessary option for admission to the EU, which Serbia is so eager to join. Deputy Chairman of the Party of United Pensioners of Serbia Konstantin Arsenovich has recently pointed out that, in principle, there was a possibility of becoming a member of the WTO, and at the same time protecting the country from genetically modified products, like some of the member countries of the EU had already done. But in this case it is necessary to develop a unified national strategy, and Serbia is, obviously, not ready for this so far

Maybe it’s time for a little human enhancement – Morally enhancing drugs added to our Water Supply

Sam de Brito

Published: December 23, 2012 – 3:00AM

‘There’s something in the water.” That’s what we say when we observe a bunch of locals behaving in the same, odd way, but maybe it’s also the answer to some of our thornier social problems?

Tap water has a host of different elements to it, including naturally occurring minerals, as well as chlorine and fluoride added by officialdom to disinfect the good drop and fortify our teeth.

It’s said if you want to quietly murder a city, poison its water supply, so it follows if you want to uplift same metropolis, why not pop some antidepressants in the drink instead?

Mass doses of psychoactive drugs might sound ridiculous at first blanch but the concept of ”morally enhancing” our population was recently aired by two professors of philosophy, from Britain’s University of Oxford and the University of Gothenburg in Sweden.

In their new book Unfit for the Future: The Urgent Need for Moral Enhancement,  Julian Savulescu and Ingmar Persson argue that while humanity’s ability to shape its environment has accelerated wildly, our morality has failed to keep pace.

”Where our ancestors’ tools shaped the few acres on which they lived, the technologies we use today have effects across the world, and across time, with the hangovers of climate change and nuclear disaster stretching far into the future,” the professors write.

”The pace of scientific change is exponential, but has our moral psychology kept up?”

A quick glance at human history shows it’s always been easier for us to harm others than to help them. For this reason, we developed a sense of morality that makes us feel bad when we hurt the people closest to us; in our family, tribe or village.

Unfortunately, that’s often where it ends. But  our actions as consumers and citizens can adversely affect far more people through environmental degradation and climate change, as well as our  apathy to wars where people who don’t look like us are dying.

Humanity’s tendency to focus on the near future and those closest to us also means political leaders are loath to force voters into painful compromises (carbon tax, anyone?) because we just don’t feel a strong enough sense of altruism about strangers in distant lands.

Savulescu and Persson speculate this is where ”moral enhancement” could be used in future. ”Our knowledge of human biology – in particular genetics and neurobiology – is beginning to enable us to directly affect the biological or physiological bases of human motivation, either through drugs, or genetic selections or engineering,” they write in Philosophy Now.

”We could use these techniques to overcome the moral and psychological shortcomings that imperil the human species”, i.e. you don’t give a crap about climate change? We’ll put something in the water to make sure you do care.

Before you start screaming Brave New World, consider how many human ”enhancements” we already embrace – from prosthetic limbs and vaccines to genetic modifications.

Others might argue better moral education is the answer but if the teachings of Buddha, Confucius, Socrates, Jesus and Kant haven’t made an impression, I’m sceptical Mrs Stringbag’s high school ethics class is going to cut much ice. Or save the polar ice caps from melting.

Tap water with your meal, sir

v

These reports are done with the appreciation of all the Doctors, Scientist, and other Medical Researchers who sacrificed their time and effort. In order to give people the ability to empower themselves. Without base aspirations of fame, or fortune. Just honorable people, doing honorable things.

Vectorproof[1]

Health Research Report

145th Issue Date 28 DEC 2012

Compiled By Ralph Turchiano

www.vit.bz

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Regular aspirin use 10 or more years ago associated with increased risk of type of age-related macular degeneration

Contact: Susan Lampert Smith slsmith2@wisc.edu 608-262-7335 JAMA and Archives Journals

CHICAGO ‑ Among nearly 5,000 study participants, regular aspirin use reported ten years prior was associated with a small but statistically significant increase in the risk of neovascular age‑related macular degeneration, according to a study in the December 19 issue of JAMA.

“Aspirin use in the United States is widespread, with an estimated 19.3 percent of adults reporting regular consumption, and reported use increases with age,” according to background information in the study. “The results of cross-sectional studies of aspirin use and its relation to age-related macular degeneration (AMD) have been inconsistent. AMD is a potentially blinding condition for which prevalence and incidence are increasing with the increased survival of the population, and regular use of aspirin is common and becoming more widespread in persons in the age range at highest risk for this disease. Therefore, it is imperative to further examine this potential association.”

Barbara E. K. Klein, M.D., M.P.H., of the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues conducted a study to examine the association between aspirin use and AMD. The researchers used data from the Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (n = 4,926) were 43 to 86 years of age at entry in the study. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. The average duration of follow-up was 14.8 years.

For the study, the researchers measured the incidences of different types of AMD (early, late, and 2 subtypes of late AMD [neovascular AMD and pure geographic atrophy]).

There were 512 incident cases of early AMD and 117 incident cases of late AMD over the course of the study. The researchers found that regular use of aspirin use 10 years prior to the retinal examination was associated with late AMD (age- and sex-adjusted incidence, 1.8 percent for users vs. 1.0 percent for nonusers). When examining the relationships by late AMD subtype, neovascular AMD was significantly associated with such use (age-and sex-adjusted incidence, 1.4 percent for users vs. 0.6 percent for nonusers), but not for pure geographic atrophy. Aspirin use 5 years or 10 years prior to retinal examination was not associated with incident early AMD.

“Our findings are consistent with a small but statistically significant association between regular aspirin use and incidence of neovascular AMD. Additional replication is required to confirm our observations. If confirmed, defining the causal mechanisms may be important in developing methods to block this effect to prevent or retard the development of neovascular AMD in persons who use aspirin, especially to prevent CVD,” the authors conclude

Ingredient in red wine may prevent some blinding diseases

2010 study posted for filing

 

Resveratrol inhibits formation of damaging blood vessels in mouse retina

By Jim Dryden

 

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.

 

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.

Compound found in rosemary protects against macular degeneration in laboratory model

Contact: Heather Buschman, Ph.D. hbuschman@sanfordburnham.org 858-795-5343 Sanford-Burnham Medical Research Institute

Sanford-Burnham researchers discover that carnosic acid, a component of the herb rosemary, promotes eye health in rodents—providing a possible new approach for treating conditions such as age-related macular degeneration

      IMAGE:   Left: This shows control cells exposed to hydrogen peroxide. Right: This shows cells treated with carnosic acid are protected from hydrogen peroxide. Live cells are stained green, dead cells are…Click here for more information.

 

LA JOLLA, Calif., November 27, 2012 – Herbs widely used throughout history in Asian and early European cultures have received renewed attention by Western medicine in recent years. Scientists are now isolating the active compounds in many medicinal herbs and documenting their antioxidant and anti-inflammatory activities. In a study published in the journal Investigative Ophthalmology & Visual Science, Stuart A. Lipton, M.D., Ph.D. and colleagues at Sanford-Burnham Medical Research Institute (Sanford-Burnham) report that carnosic acid, a component of the herb rosemary, promotes eye health.

Lipton’s team found that carnosic acid protects retinas from degeneration and toxicity in cell culture and in rodent models of light-induced retinal damage. Their findings suggest that carnosic acid may have clinical applications for diseases affecting the outer retina, including age-related macular degeneration, the most common eye disease in the U.S.

Age-related macular degeneration

Age-related macular degeneration likely has many underlying causes. Yet previous studies suggest that the disease might be slowed or improved by chemicals that fight free radicals—reactive compounds related to oxygen and nitrogen that damage membranes and other cell processes.

Lipton’s team first discovered a few years ago that carnosic acid fights off free radical damage in the brain. In their latest study, Lipton and colleagues, including Tayebeh Rezaie, Ph.D. and Takumi Satoh, Ph.D., initially investigated carnosic acid’s protective mechanism in laboratory cultures of retinal cells.

The researchers exposed the cells growing in the dish to hydrogen peroxide in order to induce oxidative stress, a factor thought to contribute to disease progression in eye conditions such as macular degeneration and retinitis pigmentosa. They found that cells treated with carnosic acid triggered antioxidant enzyme production in the cells, which in turn lowered levels of reactive oxygen and nitrogen species (cell-damaging free radicals and peroxides).

Rosemary’s therapeutic potential

Lipton, Rezaie, Satoh and colleagues next tested carnosic acid in an animal model of light-induced damage to photoreceptors—the part of the eye that converts light to electrical signals, enabling visual perception. As compared to the untreated group, rodents pre-treated with carnosic acid retained a thicker outer nuclear layer in the eye, indicating that their photoreceptors were protected. The carnosic acid-treated rodents also exhibited better electroretinogram activity, a measure of healthy photoreceptor function.

What’s next for carnosic acid? “We’re now developing improved derivatives of carnosic acid and related compounds to protect the retina and other brain areas from a number of degenerative conditions, including age-related macular degeneration and various forms of dementia,” said Lipton, director of Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and an active clinical neurologist.

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Note to members of the media: Please contact Heather Buschman at hbuschman@sanfordburnham.org to schedule on-site, phone, or Skype interviews with Stuart A. Lipton, M.D., Ph.D. Images are also available upon request.

This research was funded by the U.S. National Institutes of Health: Eunice Kennedy Shriver National Institute of Child Health & Human Development grant P01 HD29587; National Institute of Environmental Health Sciences grant P01 ES016738; National Institute of Neurological Disorders and Stroke grant P30 NS076411; National Eye Institute grant R01 EY05477

The study was co-authored by Tayebeh Rezaie, Sanford-Burnham; Scott R. McKercher, Sanford-Burnham; Kunio Kosaka, Nagase & Co., Ltd.; Masaaki Seki, Sanford-Burnham; Larry Wheeler, Allergan, Inc.; Veena Viswanath, Allergan, Inc.; Teresa Chun, Allergan, Inc.; Rabina Joshi, Sanford-Burnham; Marcos Valencia, Sanford-Burnham; Shunsuke Sasaki, Iwate University; Terumasa Tozawa, Iwate University; Takumi Satoh, Sanford-Burnham and Iwate University; and Stuart A. Lipton, Sanford-Burnham.

About Sanford-Burnham Medical Research Institute

Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org.

Macular Degeneration drugs may do More harm than good ( anti-VEGF drugs )

Scripps Research Institute Study Suggests Caution and Further Studies on Drugs Used to Treat Macular Degeneration

LA JOLLA, CA – October 24, 2012 – Millions of people with “wet” macular degeneration are prescribed a class of medication known as anti-VEGF drugs. But now scientists at The Scripps Research Institute (TSRI) have found that a drastic reduction of VEGF activity may do more harm than good.

In the new study, the researchers deleted the gene for the blood-vessel growth factor VEGF, which has been implicated in stimulating abnormal blood vessel growth in a range of cancers and eye diseases, from cells in the retinas of adult mice. The results showed that without VEGF a large subset of light-sensing cells lost their main blood supply and shut down, causing severe vision loss.

“It’s becoming clear that VEGF has a critical function in maintaining the health of the retina, and we need to preserve that critical function when we treat VEGF-related conditions,” said TSRI Professor Martin Friedlander, MD, PhD, senior author of the new study, which appears in the November 2012 issue of the Journal of Clinical Investigation.

Major Target for Drug Developers

VEGF (vascular endothelial growth factor) has long been a major target for drug developers. Tumors often overproduce VEGF to stimulate local blood vessel growth and thus keep their fast-dividing cells well supplied with oxygen and nutrients. Low-oxygen conditions in the eyes of elderly or diabetic individuals also can trigger the overproduction of VEGF, resulting in a vision-destroying bloom of abnormal, leaky retinal blood vessels.

Several anti-VEGF drugs (such as Lucentis® (ranibizumab), Macugen (pegaptanib), Eylea® (aflibercept) and Avastin® (bevacizumab)) are already in use, and dozens more are in clinical trials against cancers and common eye disorders such as wet macular degeneration.

However, to date there have not been extensive studies on the effects of such drugs on the normal role of VEGF, in part because it is hard to generate adult animals that lack the VEGF gene. When the gene is removed from the embryos of mice, in a standard“knockout” experiment, the mice fail to develop normally and die before birth.

New Insights

In the new study, Friedlander laboratory postdoctoral fellows Toshihide Kurihara, MD, PhD, and Peter D. Westenskow, PhD, found a way to delete the major VEGF gene from mice after the animals had grown to adulthood. To determine VEGF’s role in the retina, they confined the gene deletion to the animals’ retinal pigment epithelial cells, which nourish and repair the retina and are a major retinal source of VEGF. The result suggests that VEGF does have a crucial function in the adult retina.

“Only three days after we knocked down the gene, we observed the complete deterioration of the choriocapillaris, a layer of capillaries that is a major supplier of nutrients to the outer retina, the location of the rod and cone photoreceptors,”said Kurihara.

Nearby light-sensing cone cells, which are specialized for detecting color and fine detail in visual images, also rapidly lost their function, causing pronounced vision loss in the mice. Seven months after the knockdown of the VEGF gene, the retinal damage and vision loss were still evident. “The deterioration seems irreversible if VEGF is not present,” said Westenskow.

Rod cells, which support low-light and peripheral vision, were not affected by the VEGF-gene deletion. The researchers note that cone cells may be more vulnerable because they are unusually active metabolically and may be unable to withstand a significant decrease in blood supply. Cone cells also bear receptors for VEGF molecules and thus may require direct VEGF stimulation to remain healthy. In any case, even if only cone cells died and rod cells were spared, a patient would experience severe vision loss. “You’d be defeating your purpose if you dried up the abnormal blood vessel growth but at the same time killed off the cone cells,” said Friedlander.

Paths for Future Research

Whether such side effects are happening with existing anti-VEGF treatments is unclear. While these assessments are possible, but they have been considered prohibitively expensive and invasive.

Friedlander, however, now believes such studies are necessary and plans to conduct such assessments in eye-disorder patients—who typically receive direct injections of anti-VEGF drugs to their eyes—to determine whether the drugs are causing these adverse side effects. He notes that the evaluations may be particularly necessary for a new class of anti-VEGF drugs recently approved for use in the treatment of age-related macular degeneration—drugs that are much more potent and persistent than previous anti-VEGF agents.

Fortunately, anti-VEGF drugs are not the only possible strategy for treating pathological blood vessel growth, as the new study makes clear. VEGF-related tumors and eye conditions also involve the overproduction of low-oxygen signaling proteins known as HIFs. The team found that deleting the genes for these HIFs in retinal cells largely prevents blood vessel overgrowth in a standard mouse model—without affecting the normal-level production of retinal VEGF or causing eye damage.

“In light of the present findings, other strategies for treating these eye conditions could be a possibility,” Friedlander said. “Conceivably, an anti-HIF treatment could also be combined with an anti-VEGF treatment, allowing the dose of the latter to be lowered significantly.”

The Friedlander lab, in collaboration with the laboratories of David Cheresh, PhD, and Michael Sailor, PhD, of the University of California, San Diego, has also been exploring the potential utility of inhibiting microRNAs that regulate angiogenic genes further upstream to VEGF. This work is being supported by a $10 million grant from the National Eye Institute and could lead to the development of antagonists that avoid the off-target effects of VEGF inhibitors.

In addition to Friedlander, Kurihara and Westenskow, other contributors to the study, “Targeted deletion of Vegfa in adult mice induces vision loss,” were Stephen Bravo and Edith Aguilar, both of TSRI. For more information on the paper, see http://www.jci.org/articles/view/65157.

The study was supported in part by grants from the National Eye Institute of the National Institutes of Health (EY-11254, EY-021416), the Lowy Medical Research Institute, the Manpei Suzuki Diabetes Foundation and The Japan Society for the Promotion of Science.

About The Scripps Research Institute

The Scripps Research Institute is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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For information:                     Office of Communications                             Tel: 858-784-8134                                     Fax: 858-784-8136 press@scripps.edu

 

http://www.scripps.edu/news/press/2012/20121024friedlander.html

A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration

2009 study posted for filing

Contact: Angela Colmone
acolmone@asip.org
301-634-7953
American Journal of Pathology

The ‘see food’ diet

Bethesda, MD — Current research suggests that a diet high in omega-3 fatty acids may help prevent one of the leading causes of legal blindness among the elderly. The related report by Tuo et al, “A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration,” appears in the August 2009 issue of the American Journal of Pathology.

Age-related macular degeneration (AMD), loss of vision in the center of the visual field (macula) due to retinal damage, is one of the leading causes of legal blindness among the elderly. Approximately 10% of people from 66 to 74 years of age will develop some level of macular degeneration, making it difficult for them to read or even recognize faces.

A diet high in omega-3 fatty acids has been found to protect against a variety of diseases including atherosclerosis and Alzheimer’s disease. Retrospective studies have suggested that diets high in fish oil or omega-3 fatty acids may also contribute to protection against AMD. A group led by Dr. Chi-Chao Chan at the National Eye Institute in Bethesda, MD examined the direct effect of omega-3 fatty acids on a mouse model of AMD. A diet with high levels of omega-3 fatty acids resulted in slower lesion progression, with improvement in some lesions. These mice had lower levels of inflammatory molecules and higher levels of anti-inflammatory molecules, which may explain this protective effect.

Tuo et al suggest that “a diet enriched in EPA and DHA can ameliorate the progression of retinal lesions in their mouse model of AMD” and that “the results in these mice are in line with the epidemiological studies of AMD risk reduction by long chain n-3 fatty acids.” The results “further provide the scientific basis for the application of omega-3 fatty acids and their biologically active derivatives in the prevention and treatment of AMD.” In future studies, Dr. Chan and colleagues plan to use this murine model “to evaluate [other] therapies that might delay the development of AMD.” Their ongoing projects include the “testing of systematic delivered pharmacochaperones and antioxidative molecules, as well as intraocularly delivered gene therapies.”

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This work was supported by grants from The Intramural Research Program of the National Eye Institute, the National Institutes of Health, and the American Health Assistance Foundation.

Tuo J, Ross RJ, Herzlich AA, Shen D, Ding X, Zhou M, Coon SL, Hussein N, Salem Jr N, Chan C-C: A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration. Am J Pathol 2009 175: 799-807

For press copies of the articles, please contact Dr. Angela Colmone at 301-634-7953 or acolmone@asip.org.

For more information on Dr. Chi-Chao Chan, please contact:

Office of Communication
(301) 496-5248
neinews@nei.nih.gov
National Eye Institute, NIH
Building 31, Room 6A32
31 Center Drive, MSC 2510
Bethesda, MD 20892-2510.

The American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.

Scientists successfully awaken sleeping stem cells: ” 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,”

Contact: Patti Jacobs pjacobs12@comcast.net 617-868-0077 Schepens Eye Research Institute

New hope for regenerating the human retina damaged by disease or injury

Boston, MA—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 Müller 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 Müller 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 Müller 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 Müller 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.

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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.

Repost 2008