Friday, August 27, 2010

Diet, Meds and Smoking Linked to Eye Disease Risks

Good nutrition staved off cataracts; some drugs, smoking increased vision problems, studies found

MONDAY, June 14 (HealthDay News) -- A healthy diet helps guard against cataracts, while certain medications raise the risks of this common cause of vision loss, two new studies suggest.

And a third study finds that smoking increases the risk of age-related macular degeneration, another disease that robs people of their sight.

The first study found that women who eat foods that contain high levels of a variety of vitamins and minerals may be less likely to develop nuclear cataract, which is the most common type of age-related cataract in the United States.

The study is published in the June issue of the Archives of Ophthalmology.

The researchers looked at 1,808 women in Iowa, Oregon and Wisconsin who took part in a study about age-related eye disease. Overall, 736 (41 percent) of the women had either nuclear cataracts evident from lens photographs or reported having undergone cataract extraction.

"Results from this study indicate that healthy diets, which reflect adherence to the U.S. dietary guidelines . . . are more strongly related to the lower occurrence of nuclear cataracts than any other modifiable risk factor or protective factor studied in this sample of women," Julie A. Mares, of the University of Wisconsin, Madison, and colleagues said in a news release from the journal.

The second study found that medications that increase sensitivity to the sun -- including antidepressants, diuretics, antibiotics and the pain reliever naproxen sodium (commonly sold over-the-counter as Aleve) -- increase the risk of age-related cataract.

Researchers followed-up with 4,926 participants over a 15-year period and concluded that an interaction between sun-sensitizing medications and sunlight (ultraviolet-B) exposure was associated with the development of cortical cataract.

"The medications [active ingredients] represent a broad range of chemical compounds, and the specific mechanism for the interaction is unclear," Dr. Barbara E.K. Klein and colleagues at the University of Wisconsin, Madison, said in the news release. Their report was released online in advance of publication in the August print issue of the Archives of Ophthalmology.

Because the lens of the eye develops from the same tissue layer as the skin, sun-sensitizing medications may affect the eyes as well as the skin, the researchers explained.

"Our results need to be evaluated in other populations, especially in view of the increasing frequency of sun-sensitizing medications," they concluded. "If our findings are confirmed, it would be important to examine whether the effect is greater in those with higher levels of ambient sunlight (UV-B) exposure and if dose or duration of medication use is also important."

The third study, also published online and in the August print issue of Archives of Ophthalmology, found that smoking and cholesterol levels affect the risk for early-stage age-related macular degeneration (AMD).

AMD is uncommon before age 55 but the risk increases after that age, therefore most studies focus on AMD in middle-aged and older adults, according to background information in the report.

"To our knowledge, accurate estimates of prevalence of AMD among adults younger than 40 years are lacking. Such information is important for understanding the relationships of risk factors to AMD across the age spectrum and for identifying factors that might affect this disease earlier in life," Dr. Ronald Klein, of the University of Wisconsin, Madison, and colleagues said in the news release.

The study included 2,810 people, aged 21 to 84, who were assessed for the presence and severity of drusen. These yellow or white deposits in the retina are an early sign of AMD.

Overall, early AMD was detected in 3.4 percent of the participants, with rates ranging from 2.4 percent among those aged 21 to 34 to 9.8 percent for those aged 65 and older. Besides age, additional risk factors associated with increased risk for AMD included being male, heavy smoking for a long period of time, and being hearing impaired. Elevated levels of HDL ("good") cholesterol were associated with a lower risk for AMD, the study authors noted.

The findings "demonstrate that early AMD onset may occur in midlife. Some modifiable factors [smoking status and serum HDL cholesterol level] associated with AMD in older cohorts were associated with early AMD in this cohort of middle-aged adults," the researchers concluded.

Friday, August 20, 2010

Retina Transplants from Stem Cells

Human embryonic stem cells can be coaxed into three-dimensional structures of retinal cells.

By Courtney Humphries
From Technology Review (published by MIT)


Scientists have created a three-dimensional, retina-like structure out of human embryonic stem cells that they hope could someday serve as a retinal transplant for people with macular degeneration and other diseases of the retina. Their method, published recently in Journal of Neuroscience Methods, offers a potential new source of cells for retinal transplants.
Hans Keirstead, lead author of the paper and a stem cell biologist at University of California, Irvine, says that the method is designed to provide an alternative to human fetal tissue transplants, which have been conducted on a small group of patients and have resulted in improved vision. Fetal cells are difficult to obtain and raise ethical issues. "We really wanted to build upon that technique by creating a renewable source of tissue," he says.

In this study, the researchers first created two types of cells from the human embryonic stem cells: early-stage retinal cells, and retinal pigment epithelium (RPE) cells, which provide nourishment to the cells responsible for vision in the retina. The researchers then grew these two types of cells together in a chamber designed to expose them to a gradient of concentrations of solutes and growth-promoting chemicals. The cells could form three-dimensional structures, a feat rarely achieved with stem cells.

Keirstead believes that the study points to two important strategies for creating retinal transplants: growing early retinal cells along with RPE cells, and bathing the cells in a gradually changing solution that encourages the development of three-dimensional layers of cells. His team found that this approach generated early-stage retinal cells that were on the path of differentiating into all of the various cell types in the retina.

Keirstead believes that a retinal transplant will work best when made of cells that have not fully developed. "The three-dimensional layer is purposefully young," he says. Previous studies have found that younger cells are more likely to integrate with existing tissue after transplantation, rather than die.

Robert Lanza, chief scientific officer at Advanced Cell Technologies, who was not involved in the study, says that his team discovered several years ago that, when turning human embryonic stem cells into RPE cells, other stem cells would spontaneously form layers, including patches of photoreceptors. "This paper shows that you can take advantage of this natural process, and for the first time use tissue engineering techniques to generate three-dimensional retina-like structures," he says.

But Lanza is skeptical about the clinical usefulness of such structures. "You can't just transplant a retina and restore sight," he says, because it requires making a series of complex connections with the brain. Although he says there could prove to be some advantage to using three constructs of cells, "for the moment, replacing individual cell types might be the best approach for helping patients suffering from eye disease."

Scientists have been working on several approaches to retinal transplants. One approach, led by Advanced Cell Technologies, is to turn human embryonic stem cells into RPE cells and transplant them into the retina. The therapy would work best in the early stages of degeneration to halt further progress, rather than to restore vision that is already lost. Another approach is to transplant stem cells that are in the early stages of becoming light-sensitive photoreceptors, which has demonstrated efficacy in mice.
Yet another strategy is to use young tissue instead of individual cells. Fetal tissue transplants have shown some success in animals as well as a small group of humans. A study published in 2008 found that seven out of 10 patients who received the transplants had improved vision. However, there has been debate about whether these transplants actually integrate into the existing tissue. Keirstead has conducted a series of studies in animals that he says demonstrates that transplanted tissue is functioning in the eye. If so, the strategy could be useful for later-stage degeneration, when the existing retina has lost much of its function.

For Keirstead's team, the next step is to show that tissue derived from stem cells can function properly. His lab is currently transplanting the tissue into rats to determine whether the transplants can survive and incorporate into the eye, and whether they improve the animals' vision.

Friday, August 13, 2010

Researchers Say They Created a ‘Synthetic Cell’

By NICHOLAS WADE
Published: May 20, 2010
New York Times

The genome pioneer J. Craig Venter has taken another step in his quest to create synthetic life, by synthesizing an entire bacterial genome and using it to take over a cell.

Dr. Venter calls the result a “synthetic cell” and is presenting the research as a landmark achievement that will open the way to creating useful microbes from scratch to make products like vaccines and biofuels. At a press conference Thursday, Dr. Venter described the converted cell as “the first self-replicating species we’ve had on the planet whose parent is a computer.”

“This is a philosophical advance as much as a technical advance,” he said, suggesting that the “synthetic cell” raised new questions about the nature of life.

Other scientists agree that he has achieved a technical feat in synthesizing the largest piece of DNA so far — a million units in length — and in making it accurate enough to substitute for the cell’s own DNA.

But some regard this approach as unpromising because it will take years to design new organisms, and meanwhile progress toward making biofuels is already being achieved with conventional genetic engineering approaches in which existing organisms are modified a few genes at a time.

Dr. Venter’s aim is to achieve total control over a bacterium’s genome, first by synthesizing its DNA in a laboratory and then by designing a new genome stripped of many natural functions and equipped with new genes that govern production of useful chemicals.

“It’s very powerful to be able to reconstruct and own every letter in a genome because that means you can put in different genes,” said Gerald Joyce, a biologist at the Scripps Research Institute in La Jolla, Calif.

In response to the scientific report, President Obama asked the White House bioethics commission on Thursday to complete a study of the issues raised by synthetic biology within six months and report back to him on its findings. He said the new development raised “genuine concerns,” though he did not specify them further.

Dr. Venter took a first step toward this goal three years ago, showing that the natural DNA from one bacterium could be inserted into another and that it would take over the host cell’s operation. Last year, his team synthesized a piece of DNA with 1,080,000 bases, the chemical units of which DNA is composed.

In a final step, a team led by Daniel G. Gibson, Hamilton O. Smith and Dr. Venter report in Thursday’s issue of the journal Science that the synthetic DNA takes over a bacterial cell just as the natural DNA did, making the cell generate the proteins specified by the new DNA’s genetic information in preference to those of its own genome.

The team ordered pieces of DNA 1,000 units in length from Blue Heron, a company that specializes in synthesizing DNA, and developed a technique for assembling the shorter lengths into a complete genome. The cost of the project was $40 million, most of it paid for by Synthetic Genomics, a company Dr. Venter founded.

But the bacterium used by the Venter group is unsuitable for biofuel production, and Dr. Venter said he would move to different organisms. Synthetic Genomics has a contract from Exxon to generate biofuels from algae. Exxon is prepared to spend up to $600 million if all its milestones are met. Dr. Venter said he would try to build “an entire algae genome so we can vary the 50 to 60 different parameters for algae growth to make superproductive organisms.”

On his yacht trips round the world, Dr. Venter has analyzed the DNA of the many microbes in seawater and now has a library of about 40 million genes, mostly from algae. These genes will be a resource to make captive algae produce useful chemicals, he said.

Some other scientists said that aside from assembling a large piece of DNA, Dr. Venter has not broken new ground. “To my mind Craig has somewhat overplayed the importance of this,” said David Baltimore, a geneticist at Caltech. He described the result as “a technical tour de force,” a matter of scale rather than a scientific breakthrough.

“He has not created life, only mimicked it,” Dr. Baltimore said.

Dr. Venter’s approach “is not necessarily on the path” to produce useful microorganisms, said George Church, a genome researcher at Harvard Medical School. Leroy Hood, of the Institute for Systems Biology in Seattle, described Dr. Venter’s report as “glitzy” but said lower-level genes and networks had to be understood first before it would be worth trying to design whole organisms from scratch.

In 2002 Eckard Wimmer, of the State University of New York at Stony Brook, synthesized the genome of the polio virus. The genome constructed a live polio virus that infected and killed mice. Dr. Venter’s work on the bacterium is similar in principle, except that the polio virus genome is only 7,500 units in length, and the bacteria’s genome is more than 100 times longer.

Friends of the Earth, an environmental group, denounced the synthetic genome as “dangerous new technology,” saying that “Mr. Venter should stop all further research until sufficient regulations are in place.”

The genome Dr. Venter synthesized is copied from a natural bacterium that infects goats. He said that before copying the DNA, he excised 14 genes likely to be pathogenic, so the new bacterium, even if it escaped, would be unlikely to cause goats harm.

Dr. Venter’s assertion that he has created a “synthetic cell” has alarmed people who think that means he has created a new life form or an artificial cell. “Of course that’s not right — its ancestor is a biological life form,” said Dr. Joyce of Scripps.

Dr. Venter copied the DNA from one species of bacteria and inserted it into another. The second bacteria made all the proteins and organelles in the so-called “synthetic cell,” by following the specifications implicit in the structure of the inserted DNA.

“My worry is that some people are going to draw the conclusion that they have created a new life form,” said Jim Collins, a bioengineer at Boston University. “What they have created is an organism with a synthesized natural genome. But it doesn’t represent the creation of life from scratch or the creation of a new life form,” he said.