Diabetic retinopathy is the leading cause of vision loss among patients with diabetes. The disease is caused by the unwanted growth of capillary cells in the retina, which in its advanced stages can result in blindness.
The drug delivery mechanism is detailed in the current issue of Lab on a Chip, a multidisciplinary journal on innovative microfluidic and nanofluidic technologies.
The lead authors are recent PhD mechanical engineering graduate Fatemeh Nazly Pirmoradi, who completed the study for her doctoral thesis, and Mechanical Engineering Associate Professor Mu Chiao, who studies nanoscience and microelectromechanical systems for biological applications.
“We wanted to come up with a safe and effective way to help diabetic patients safeguard their sight,” says Prof. Chiao, who has a family member dealing with diabetic retinopathy.
A current treatment for diabetic retinopathy is laser therapy, which has side effects including laser burns or the loss of peripheral or night vision.Anti-cancer drugs may also be used to treat the disease. However, these compounds clear quickly from the bloodstream so high dosages are required, thus exposing other tissues to toxicity.
Key to UBC’s innovation is the ability to trigger the drug delivery system through an external magnetic field.The team accomplished this by sealing the reservoir of the implantable device—which is no larger than the head of a pin—with an elastic magnetic polydimethylsiloxane (silicone) membrane. A magnetic field causes the membrane to deform and discharge a specific amount of the drug, much like squeezing water out of a flexible bottle.
In a series of lab tests, the UBC researchers loaded the implantable device with the drug docetaxel and triggered the drug release at a dosage suitable for treating diabetic retinopathy.They found that the implantable device kept its integrity with negligible leakage over 35 days.
They also monitored the drug’s biological effectiveness over a given period, testing it against two types of cultured cancer cells, including those found in the prostate. They found that they were able to achieve reliable release rates. The docetaxel retained its pharmacological efficacy for more than two months in the device and was able to kill off the cancer cells,” says Dr. Pirmoradi.
The UBC device offers improvements upon existing implantable devices for drug delivery, says Prof.Chiao. “Technologies available now are either battery-operated and are too large for treating the eye, or they rely on diffusion, which means drug release rates cannot be stopped once the device is implanted—a problem when patients’ conditions change.”
Dr. Pirmoradi says it will be several years before the UBC device is ready for patient use: “There’s a lot of work ahead of us in terms of biocompatibility and performance optimization.”
The team is also working to pinpoint all the possible medical applications for their device so that they can tailor the mechanical design to particular diseases.
Murocel Lot Recalled
Bausch + Lomb is voluntarily recalling a single lot of Murocel Methylcellulose Lubricant Ophthalmic Solution, USP 1%, only available within the United States. (Expiry date: 1-31-2012)
The recall was based on routine stability testing that showed the single lot was out of specification for preservative efficacy. There have been no adverse events reported. Murocel is an over-the-counter ophthalmic solution indicated for the temporary relief of burning and irritation due to dry eye, has been available in the United States for more than a decade.Consumers may call B + L customer service for instructions on returning and reimbursement: 1-800-553-5340.
Lifestyle, Diet Impact Course of AMD
Eating a diet high in vitamin D, as well as the nutrients betaine and methionine, might help reduce the risk of macular degeneration, according to
new research conducted by Tufts Medical Center scientists. Their study
of identical twins from the U.S. World War II Twin Registry also found
that the more a person smoked, the higher his risk of developing macular
degeneration.
The study, “ Smoking, Dietary Betaine, Methionine, and Vitamin D in Monozygotic Twins with Discordant Macular Degeneration: Epigenetic Implications” published in July’s Ophthalmology, is the first to look at identical twin pairs in which one twin had early age-related macular degeneration, and the other had late stage AMD.
AMD is highly heritable, with genetic factors determining up to 71 percent of the disease’s severity as determined by a previous study of this twin registry by this same research team. By examining identical twins with the same genes but whose disease was at different stages, researchers were able to identify environmental and behavioral factors that may contribute to the severity of the disease.“We wanted to know why, if they have the same genes, do they have different stages of the disease?’’ said lead researcher Johanna M. Seddon, MD, ScM, director of the Epidemiology and Genetics Service, Tufts Medical Center, and professor of ophthalmology, Tufts University School of Medicine.
“Eat a healthy diet with lots of fruits and vegetables, and that can make a difference—even if you have a genetic susceptibility to macular degeneration,’’ said Dr. Seddon, a specialist in macular degeneration, “and, of course, don’t smoke.’’
The study, “ Smoking, Dietary Betaine, Methionine, and Vitamin D in Monozygotic Twins with Discordant Macular Degeneration: Epigenetic Implications” published in July’s Ophthalmology, is the first to look at identical twin pairs in which one twin had early age-related macular degeneration, and the other had late stage AMD.
AMD is highly heritable, with genetic factors determining up to 71 percent of the disease’s severity as determined by a previous study of this twin registry by this same research team. By examining identical twins with the same genes but whose disease was at different stages, researchers were able to identify environmental and behavioral factors that may contribute to the severity of the disease.“We wanted to know why, if they have the same genes, do they have different stages of the disease?’’ said lead researcher Johanna M. Seddon, MD, ScM, director of the Epidemiology and Genetics Service, Tufts Medical Center, and professor of ophthalmology, Tufts University School of Medicine.
“Eat a healthy diet with lots of fruits and vegetables, and that can make a difference—even if you have a genetic susceptibility to macular degeneration,’’ said Dr. Seddon, a specialist in macular degeneration, “and, of course, don’t smoke.’’
Each twin completed a questionnaire about nutritional and health behaviors. The study found that twins whose macular degeneration was at the early stages tended to consume more vitamin D from dietary sources such as fish or milk than their brothers.Vitamin D may reduce the risk of macular degeneration because it has anti-inflammatory properties. It may also block the formation of new blood vessels that can grow under the macula, leaking blood and causing vision loss in the more severe stages of the disease. Similarly, Dr. Seddon’s research team also found that higher intakes of betaine and methionine were linked to a slower progression of the disease. These nutrients have also been linked to epigenetic mechanisms, which is a change in DNA, not attributable to a change in the actual DNA sequence. Betaine is found in fish, grains and spinach, while methionine is found in poultry, fish and dairy foods.
The study also found that among the pairs of twins, the twin who was the heavier smoker tended to have the more severe case of macular degeneration.These results indicate that both genetic susceptibility and environmental factors are important, that epigenetic factors may also be involved, and further underscores the importance of modifiable behaviors, especially avoiding smoking and eating a healthy diet, to help prevent or delay the progression of macular degeneration.
The study evaluated pairs of elderly male twins and used a survey of personal dietary and health habits to determine variations.
Is Oxygen Key To Higher Glaucoma Risk in Blacks?
Measuring oxygen during eye surgery, investigators at Washington University School of Medicine in St. Louis have discovered a reason that may explain why African Americans have a higher risk of glaucoma than Caucasians.
They found that oxygen levels are significantly higher in the eyes of African Americans with glaucoma than in Caucasians with the disease. They suspect that more oxygen may damage the drainage system in the eye, resulting in elevated pressure. Higher pressure can damage the optic nerve, causing blindness.
The study provides the first physiologic clue about the link between race and risk for glaucoma. Glaucoma is the leading cause of blindness among African Americans. Compared to Caucasians, glaucoma is about six times more common in African Americans, and blindness caused by glaucoma is roughly 16 times more likely in African Americans.
“Our findings suggest there may be physiologic differences in oxygen metabolism between African Americans and Caucasians,” says first author Carla J. Siegfried, MD. “In our studies, we were not looking specifically at African Americans, but the racial difference in oxygen levels was signifi - cant, and we believe this observation deserves further study.”
The researchers measured oxygen levels in the eyes of patients who were having surgery for cataracts or glaucoma or both. At the beginning of surgery, they inserted a probe to measure oxygen in five places in the front part of the eye. They took measurements near the center of the cornea; in the middle of the anterior chamber of the eye; and in the anterior chamber angle. That region is particularly important in glaucoma because that’s where fluid drains from the eye.
They also measured oxygen in two locations near the lens of the eye in patients having cataract surgery. Oxygen was significantly higher in African Americans at all five locations.
Dr. Siegfried, professor of ophthalmology and visual sciences at Washington University, says it’s not surprising that oxygen may play a big role in the development of glaucoma because it may be a source of free radicals that damage cells. Oxidative stress, an imbalance between these free radicals and antioxidants, is linked to the aging process and many other age-related conditions like cardiovascular and neurodegenerative diseases.
“We began studying oxygen in the eye after our basic studies showed that it was tightly regulated there, with the lowest levels near the lens,” says David C. Beebe, PhD, the Janet and Bernard Becker Professor of Ophthalmology and Visual Sciences and professor of cell biology and physiology.“Clinical studies with Nancy Holekamp [professor of clinical ophthalmology and visual sciences] and Ying-Bo Shui [senior scientist] revealed that exposure of the lens to excess oxygen caused the most common kind of cataracts. And our discovery about cataracts led us, somewhat surprisingly, to glaucoma. Dr. Siegfried then joined us, confirming the connection between oxygen and glaucoma, and the link between oxygen and race was yet another surprise.”
All of the patients in this study were having eye surgery, so the researchers did not have a comparison or control group. But the African-American patients having surgery often were younger than Caucasians.
“Glaucoma often affects African Americans at a younger age,” Dr. Siegfried says. “And when we used statistical methods to adjust for differences in age, the difference in oxygen levels between African Americans and Caucasians became more significant.Then, when we controlled for racial differences, we found that increased age became an important indicator of elevated oxygen levels in certain locations in the front part of the eye.”
A previously published study by Dr. Siegfried and colleagues demonstrated that oxygen levels increase in the eye following vitrectomy. This increase in oxygen has been shown to be associated with cataract development in these patients, as well as with increased, long-term risk of glaucoma.
Dr. Siegfried says it is not yet possible to say whether the elevated oxygen levels cause pressure to rise and optic nerve damage to occur, but she says higher levels of oxygen are clearly associated with factors, like race, that carry increased glaucoma risk. Her team has received a four-year grant from the National Eye Institute to further investigate that association.
Drs. Siegfried and Beebe say the next step is to extend their studies of patients and to explore the effects of elevated oxygen levels in animal models of glaucoma. They also plan to measure oxygen utilization in patients by placing a modified contact lens on the eye to measure how much oxygen is being consumed.
“It’s not that older patients or African-American patients are somehow getting more oxygen into their eyes,” Dr. Siegfried explains. “Rather, aging may result in lower oxygen consumption, leaving higher amounts in the eye.In contrast, African Americans may have more efficient oxygen metabolism, with the same result. The excess oxygen may result in the formation of oxygen byproducts that cause cellular damage. However, more study is required.When we understand the underlying reason for elevated oxygen and how it may damage the eye, we will be in a better position to develop ways to prevent this disease.”
The researchers reported their findings in the July issue of the Archives of Ophthalmology.
Drug Improves Sight for Patients with Leber’s
A clinical trial led by Newcastle University shows that the drug, idebenone (Catena), improved the vision and perception of color in patients with Leber’s hereditary optic neuropathy. In some severely affected patients such as those who were unable to read any letters on the chart, the treatment with idebenone resulted in a marked improvement in their vision. In nine patients (12 eyes) out of 36 patients (61 eyes) taking idebenone, vision improved to the extent that patients were able to read at least one row of letters on the chart. In contrast not a single patient of the 26 who were taking the placebo improved to that extent.
LHON is caused by damage to the mitochondria in the eyes. It is one of the most common causes of inherited blindness and is thought to affect around 2,000 people in the UK, around 10,000 in Europe and a further 10,000 in the United States.
Idebenone penetrates into the mitochondria and is thought to mop up toxic free radicals and enhance mitochondrial function.
