Pioneering Eye Surgeon Sees Hope for Treating Macular Degeneration with Natural Hormones

By Debora Yost

Plant caroteinoids such as lutein and zeaxanthin were long ago shown to help prevent macular degeneration. But is there more that can be done to protect against this epidemic of blindness?

George W. Rozakis, MD is a Cornell-trained biomedical engineer specializing in laser eye surgery and lens implants. A pioneer in the field of LASIK surgery,1 Dr. Rozakis is now vigorously involved in anti-aging medical research.

Dr. Rozakis is focusing on a potential breakthrough in treating macular degeneration, a condition that gradually destroys central vision. Also called age-related macular degeneration, it is the leading cause of blindness in people aged 65 and older.

Dr. Rozakis believes that restoring the correct balance of natural hormones that decline with age can retard and possibly even reverse the progression of macular degeneration. To investigate this hypothesis, he is setting up a long-term study and is currently seeking subjects to participate in the trial.
Hormones and Your Vision

The hormonal link with macular degeneration began to evolve when Dr. Rozakis met another medical pioneer, Sergey A. Dzugan, MD, PhD, during a conference in Chicago four years ago. Dr. Dzugan is a cardiovascular surgeon and internationally known expert in anti-aging and hormonal medicine.

“Dr. Dzugan has done numerous studies2-4 and written numerous articles on the association between low hormone levels and multiple disease states, including the problem of atherosclerosis and cholesterol elevation,” says Dr. Rozakis. “As an ophthalmologist I was impressed by the evidence that restoring and optimizing levels of key hormones improve brain function, largely because the retina is part of the brain. For example, there is very impressive literature that testosterone slows down the progression of Alzheimer’s disease.5 Pregnenolone is extremely important for the brain and nervous system, as are progesterone and estrogens. Women whose progesterone levels drop develop negative personality changes.6 In animal models, pregnenolone and DHEA have been shown to profoundly stimulate the healing of neurologic injury.7-9 Women who enter into menopause at a young age develop macular degeneration, presumably because of the absence of estrogens.10,11 Blocking estrogens with the anti-cancer drug tamoxifen is harmful to the retina.12 This leads us to wonder if optimal hormonal health also positively impacts ocular health.”

“When an article appeared in the American Journal of Ophthalmology indicating that DHEA, or dehydroepiandrosterone, is exceptionally low in macular degeneration patients,13 I was shocked and excited,” says Dr. Rozakis. This finding provided a major clue that hormonal imbalance was part of the problem of macular degeneration.

“DHEA is like the Grand Central Station of hormone chemistry,” says Dr. Rozakis. “When DHEA levels drop, it strongly implies that levels of other hormones such as pregnenolone, estrogens, and testosterone are out of balance or suboptimal.” All of these hormones make the body thrive—they give us virility, fertility, and help us act and react quicker. Since the retina contains hormone receptors, hormones must be part of the biophysiology of vision itself.
Cardiovascular Link

Low DHEA levels in macular degeneration could also explain its association with heart disease, as it is known that macular degeneration is an independent risk factor for stroke and coronary artery disease. In a study conducted by Australian scientists,14 macular degeneration predicted a five-fold higher risk of cardiovascular mortality and a 10-fold higher risk of stroke mortality. After controlling for traditional cardiovascular risk factors, age-related macular degeneration predicted a doubling of cardiovascular mortality. Since hormone deficiency has been linked with both heart disease and eye disorders,13,15 it is a prime suspect that links the heart to the eye.

Further examination of the literature reveals a major review article from Italy that explains the importance of hormones to the retina.16 In this article, it is shown that the retina is able to attempt to make its own hormones, just like the brain. “The article also indicates that many of the hormones we use in anti-aging programs have a role in the retina, such as pregnenolone, DHEA, testosterone, estrogens, and progesterone. Few ophthalmologists and optometrists are aware of this relationship. This was the smoking gun that led to our hypothesis,” Dr. Rozakis notes.
Macular Degeneration and Cholesterol

A good theory needs to connect all the dots. Dr. Rozakis explains that one challenge in shaping his theory was explaining the presence of “drusen” or spots that appear in the retina in patients with macular degeneration. Many consider these spots to be “degradation products.”

Recently, Goldis Malek, PhD, and others17-19 found that cholesterol was present in those spots. This led some people to think that cholesterol-lowering agents, such as statins, might help macular degeneration—but they do not. In fact, there is concern that statins actually increase the risk of dry macular degeneration advancing to the neovascular form of the disease, whereby tiny blood vessels in the eye begin to bleed.20

Dr. Rozakis notes, “To Dr. Dzugan and me, the presence of cholesterol in the macula was the key piece of data that integrated everything. The presence of cholesterol in the macula suggests that the retina is trying to make hormones—but that it can’t. So, the body’s accumulation of cholesterol and drusen worsen.” He continues, “The macula can’t get the hormones it needs from the blood because there aren’t much there. As a result, if the macula is having trouble converting cholesterol into hormones, drusen form, and this results in the drusen we see in macular degeneration. Why the macula stops making hormones is unknown, but it is associated with aging. We can speculate that it happens because the enzymes which do the conversion decrease or are down-regulated with aging.”

“This same ‘story’ of cholesterol and hormones plays itself out in the body as a whole,” says Dr. Rozakis. “We do know that the adrenal gland, which produces DHEA, loses the ability to manufacture hormones as we age. As Dr. Dzugan published, this hormonal decline stimulates the liver to produce more cholesterol in an attempt to create more hormones.3 This is why restoring hormones to their normal levels causes the liver to produce less cholesterol. That same paradigm may be happening in the macula. This is the basis of our hypothesis. The goal therefore must be to provide the retina the hormones it needs through supplementation.”
Reviewing the Evidence

There is already evidence to support the notion that DHEA protects the eyes against oxidative damage21 and that the hormone pregnenolone improves electrical activity in the retina, as measured by the electroretinogram (ERG).22,23 There is also evidence to support the use of melatonin in the treatment of macular degeneration.24,25

The theory that optimizing hormones may help promote macular health is based on these scientific facts:

1.The macula, which is located in the center of the retina, uses hormones to function.16
2.The normal macula has the unique ability to make its own hormones.26
3.The bloodstream of patients with macular degeneration is deficient in hormones.11,13
4.Drusen—the tiny yellow abnormalities that appear behind the macula in individuals with macular degeneration—contain cholesterol.17-19
5.Age-related macular degeneration is related to cardiovascular mortality.14

Dr. Rozakis speculates that the solution for treating macular degeneration is to measure and restore age-depleted hormones to optimal levels so that the macula can absorb the hormones it needs from the blood. “Hopefully restoring hormones to their normal levels in the bloodstream will cause the macula to stop absorbing cholesterol and, as a result, drusen formation will hopefully decline,” says Dr. Rozakis. “We certainly need a better understanding of the pathophysiology of this blinding disease.”27
A Higher Level of Natural Treatment

Dr. Rozakis sees hormone restoration as a strategy to improve on existing studies showing that certain nutrients can reduce the progression of age-related macular degeneration. The long-term Age-Related Eye Disease Study (AREDS), conducted by the National Eye Institute, found that supplementing the anti-oxidants beta-carotene, vitamin C, vitamin E, and the mineral zinc reduced the risk of developing advanced states of macular degeneration in more than 4,700 high-risk patients aged 55 to 80 who were enrolled in the study.28

The specific amounts of nutrients used by the study researchers were:

*500 mg of vitamin C
*400 IU of vitamin E
*15 mg of beta-carotene
*80 mg of zinc
*2 mg of copper.

The copper, administered as cupric oxide, was included in the formula to prevent copper-deficiency anemia, which is associated with high zinc intake.

As a result of the AREDS trial, many ophthalmologists are recommending supplements containing the study’s recommended dosages for patients with or at a high risk for age-related macular degeneration.

Dr. Rozakis is currently developing his own study to test his theory concerning the relationship between low levels of DHEA and macular degeneration. “Our study is going to focus on overall hormonal balance and will include the supplements used in the AREDS study as well,” says Dr. Rozakis. “Our goal is to do everything we can to stop macular degeneration. The fact that hormones are much more powerful than vitamins holds hope that the results will be significant.”

If you have any questions on the scientific content of this article, please contact a Life Extension Health Advisor at 1-800-226-2370.

Macular Degeneration Can Disappear with Natural Therapies

Filed Under Dr. Zoltan Rona (MD) |

Macular degeneration is the leading cause of visual loss in Europeans and North Americans over the age of 50. It is thought to be the direct result of free radical damage to the macula, a small area located at the centre of the retina. The macula is responsible for fine vision.

Patient Profile:

A 79-year-old woman recently consulted me because a top expert in eye diseases diagnosed her as having macular degeneration. She was told that nothing could be done and, to quote the specialist, “You are going to go blind.”

As it turns out, this was not only discouraging for my patient, but a completely wrong prediction.

Here’s the advice I gave this patient:

Diet

• Eat more legumes, which have a cleansing effect due to their high content of sulphur-containing amino acids.
• Consume more fresh fruits and vegetables, especially yellow vegetables.
• Berries are wonderful—particularly blueberries because of their high content of anthocyanidins.
• Cherries are valuable because they offer carotenes, flavonoids, and vitamins E and C.
• Carotenoids—lutein and zeaxanthin—are most strongly associated with reduced risk of macular degeneration. The best sources are spinach, kale, and collard greens.

Supplements

None of these natural supplements have any serious side effects. Take the following antioxidant supplements each day:

• Beta-carotene: 100,000 IU
• Green powder: Choose an enzymatically active green “superfood” powder. Green products are high in carotenoids. Take 1 tablespoon in 15 ml of water or juice.
• Vitamin C: 2,000 mg three times daily
• Pycnogenol: 300 mg (from either pine bark extract or grape seed extract)
• Coenzyme Q10: 100 mg three times daily
• Vitamin E: 400 IU three times daily
• Selenium: 600 mcg
• Zinc chelate or citrate: 100 mg. Several published studies support the use of zinc supplements to help reverse numerous eye disorders including macular degeneration.

Botanicals

Research reveals that the following botanical medicines also show impressive results with macular degeneration:

• Ginkgo biloba extract: 250 mg
• Bilberry extract: 80 mg twice daily (25% anthocyanidin content). Bilberry is used in Europe for cataracts, macular degeneration, retinitis pigmentosa, and diabetic retinopathy. It can also prevent further damage from glaucoma by working as an antioxidant in the eyes. Its anthocyanidins increase vitamin C levels (a critical nutrient for healthy eyes) within the cells and decrease capillary fragility.

Result

A six-month follow-up visit to the eye specialist showed complete clearing of this patient’s macular degeneration.

Dr. Zoltan Rona

Macular degeneration patients treated with cancer drug show problems

Last Updated: Friday, December 5, 2008 | 10:21 AM ET

The Canadian Press

The colon cancer drug Avastin is used off-label to treat wet AMD. (CBC)

Public health authorities in Canada are investigating a spike in cases of eye inflammation among patients being treated for macular degeneration with the cancer drug Avastin.

First noticed in British Columbia, there appears to be a rise in cases in other parts of the country as well. And now authorities are trying to draw the potential problem to the attention of the global public health community in the hopes of seeing if it is being observed elsewhere.

The problem is believed to stem from a particular lot of the drug that was distributed widely around the world, though not to the United States. The lot number is B3002B028.

The drug's manufacturer, the Swiss pharmaceutical firm Roche, is co-operating with Health Canada and the British Columbia Centre for Disease Control, which was alerted to the problem by ophthalmologists.

The situation puts Roche in an awkward position. Avastin (bevacizumab) is a colon cancer drug; it is not approved for use as a treatment age-related macular degeneration.

And Roche doesn't want to encourage the off-label use of the drug by ophthalmologists who have embraced it as a much cheaper alternative to a similar drug, Lucentis, which has been approved as a treatment for macular degeneration.

"Absolutely we do not recommend this," said Samantha Ouimet, a spokesperson for Roche Canada. "They're taking it out of its [original] packaging, repackaging it and injecting it into people's eyes. This comes in a bag and it's meant for intravenous use for people with cancer."

Ouimet said the company is in discussions with Health Canada. But it is reluctant to put out an advisory warning people not to use the drug as a treatment for age-related macular degeneration when the drug was never approved for this purpose.

Any statement could be seen as promoting the off-label use, Ouimet said.

"Is it a delicate situation? Absolutely."

B.C. cluster investigated

Ophthamologists in British Columbia started noticing a problem in October. Under two per cent of people treated for age-related macular degeneration with Avastin will develop acute intra-ocular inflammation. But between Oct. 3 and Oct. 27, the rates were much higher.

The BC CDC was called in to help investigate the cluster of cases, and concluded the rate of inflammation among patients treated with Avastin from the lot in question was almost 10 times higher than the normal rate. The lot is no longer in use there.

Dr. David Patrick, the centre's director of epidemiology services, submitted a report on the investigation to ProMED, an electronic reporting system that sends out alerts about outbreaks to a mailing list of public health officials, scientists and other interested parties around the world.

No problems reported in other countries

Patrick said the team investigating the issue sent out feelers to ophthamologists in about a half-dozen other Canadian centres and has heard back that others too have noticed an increase in cases of inflammation after use.

The inflammation causes cloudy vision, but appears to clear up over time, he said.

Ouimet said there have been no reports of problems from other countries — and no reports of adverse reactions in cancer patients who received treatments from the same lot.

"We have reviewed all the analytical release data for the lot in question. And all the best parameters were within the limits for use in oncology," she said.

"So we found no deviations in the manufacturing process. All the environmental testing was fully compliant. We've revisited the batch. It is safe … for its indicated purpose."

Patrick said scientists at the University of British Columbia are studying vials of the drug, but haven't found anything usual.

"On the initial go-through they haven't determined a chemical difference between the implicated lot and another one. But there may well be further work with that," he said.

Treatment of Macular Degeneration Looks Promising After New Study

It may now be possible to trigger the regeneration of inner nerve cells in a damaged mammalian retina, according to researchers from The University of Washington.

Writing about their findings in the Proceedings of the National Academy of Sciences, the researchers revealed that they studied a particular retinal cell called the Muller glia.

"This type of cell exists in all the retinas of all vertebrates, so the cellular source for regeneration is present in the human retina," said lead researcher Tom Reh, a professor of Biological Structure at the university.

He said that developing certain methods to re-generate such cells might lead to new treatments for vision loss from retina-damaging diseases, like macular degeneration.

The researchers pointed out that cold-blooded vertebrates like fish have a remarkable ability to regenerate their retinas after damage, while Birds that are warm-blooded have some limited ability to regenerate retinal nerve cells after exposure to nerve toxins.

While fish can generate all types of retinal nerve cells, the researcher said, chicks produce only a few types of retinal nerve cell replacements, and few receptors for detecting light.

After a baby's eyes pass a certain developmental stage, Muller glia cells generally stop dividing.

According to the researchers, damage to retinal cells in both fish and birds prompts the specialized Muller glia cells to start dividing again, and to increase their options by becoming a more general type of cell called a progenitor cell. They say that such progenitor cells can then turn into any of several types of specialized nerve cells.

The researchers say that mammals have an even more limited Muller glia cell response to injury, compared to birds. They suggest that in an injured mouse or rat retina, the cells may react and become larger, but few start dividing again.

The team points out that several research groups have tried to stimulate the Muller glia cells to grow in lab dishes and in lab animals by injecting cell growth factors or factors that re-activate certain genes that were silenced after embryonic development.

Observations made during such studies suggested that the Muller glia cells could be artificially stimulated to start dividing again, and to show light-detecting receptors.

However, all those studies had failed to detect any regenerated inner retina nerve cells, except when the Muller glia cells were genetically modified with genes that specifically promote the formation of amacrine cells, which act as intermediaries in transmitting nerve signals.

"This was puzzling, because in chicks amacrine cells are the primary retinal cells that are regenerated after injury," Reh said.

With a view to resolving the discrepancy between what was detected in chicks and not detected in rodents, the researchers carried out a systematic analysis of the response to injury in the mouse retina, and the effects of specific growth factor stimulation on the proliferation of Muller glia cells.

They injected a substance into the retina to eliminate ganglion cells, a type of nerve cell found near the surface of the retina, and amacrine cells. Then by injecting the eye with epidermal growth factor (EGF), fibroblast growth factor 1 (FGF1) or a combination of FGF1 and insulin, they were able to stimulate the Muller glia cells to re-start their dividing engines and begin to proliferate across the retina.

The proliferating Muller glia cells first transformed into unspecialised cells, something that the researchers were able to detect by checking for chemical markers that indicate progenitor cells.

Soon some of the general cells changed into amacrine cells, and the researchers detected their presence by checking for chemicals produced only by amacrine cells.

The researchers observed that many of the progenitor cells arising from the dividing Muller glia cells died within the first week after their production, but those that managed to turn into amacrine cells survived for at least 30 days.

"It's not clear why this occurs, but some speculate that nerve cells have to make stable connections with other cells to survive," the researchers wrote.

Source-ANI

Osiris completes enrollment in Phase III GVHD trial

Dec 05, 2008 (Datamonitor via COMTEX)

Osiris Therapeutics, a stem cell therapeutic company, has completed patient enrollment in its Phase III pivotal trial evaluating Prochymal for the treatment of steroid-refractory acute graft versus host disease.

This double-blinded, placebo controlled trial will assess safety and efficacy of Prochymal over a six-month period. A total of 244 patients were enrolled at 72 leading bone marrow transplant centers across the US, Canada, the UK, Spain, Italy, Australia, Germany and Switzerland.

In total, 168 patients were treated in the US, 31 in Canada, 27 in Europe, and 18 in Australia. A total of 27 pediatric patients were enrolled. The last patient is expected to complete the trial by May 29, 2009.

Prochymal is a proprietary formulation of adult mesenchymal stem cells designed to provide therapeutic benefit by controlling inflammation, promoting tissue regeneration, and preventing scar formation.

Osiris and Genzyme have previously announced a strategic alliance for the development and commercialization of Prochymal. Under the terms of the agreement, Osiris will commercialize Prochymal in the US and Canada, and Genzyme will commercialize the treatment in all other countries.

Moya Daniels, study director for the steroid-refractory graft versus host disease (GVHD) program at Osiris, said: "On behalf of everyone at Osiris, I would like to offer our sincere appreciation to the patients, their families, and all of the outstanding healthcare professionals who participated in this historic event. We look forward with great anticipation to the results of this landmark stem cell trial and the opportunity to make a positive difference in the care of transplant patients everywhere."