“That’s the dream, and this is a big step,” said Rachel Martin, PhD, UC Irvine associate professor of chemistry and co-author of a paper featured in the December issue of the journal Structure. “Understanding the molecular mechanism of what goes wrong in the eye that leads to a cataract could lead to the development of better treatment options, including more sophisticated artificial lenses and drugs.”
It has long been known that human eyes have a powerful ability to focus because of three kinds of crystallin proteins in their lenses, maintaining transparency via a delicate balance of both repelling and attracting light. Two types of crystallin are structural, but the third—dubbed a “chaperone”—keeps the others from clumping into cataracts if they’re modified by genetic mutation, ultraviolet light or chemical damage.
The UC Irvine team painstakingly explored and identified the structures of the normal proteins and a genetic mutation known to cause cataracts in young children. They found that the chaperone proteins bind far more strongly to the mutated proteins in an effort to keep the lens clear. One major problem: Every human eye contains a finite number of the helpful proteins. Once they’re used up, the researchers learned, weakened ones quickly begin to aggregate and form blinding cataracts.
Now that this mechanism has been mapped at the molecular level, the team is hopeful that organic chemists can create sight-saving treatments to prevent such aggregation.
While people with adequate medical care can have corrective surgery for cataracts, the World Health Organization has found that millions suffer major vision loss because they do not have access to laser surgery or other options. By 2019, the number of people older than 50 with impaired sight is expected to grow even higher, particularly in China, India, Southeast Asia and Eastern Mediterranean nations.
Novel Removal Method May Mean Stem Cell Advance
Researchers in the Cedars-Sinai Regenerative Medicine Institute have designed and tested a novel, minute-long procedure to prepare human amniotic membrane for use as a scaffold for specialized stem cells that may be used to treat some corneal diseases. This membrane serves as a foundation that supports the growth of stem cells in order to graft them onto the cornea.
This new method, explained in a paper published this month in the journal PLoS ONE, may accelerate research and clinical applications for stem cell corneal transplantation.
An approved biological foundation for cultured stem cells is the human amniotic membrane. For the best growth of stem cells, amniotic cells need to be removed by chemical agents. The existing methods for removing these cells from this membrane are not standardized, leave behind amniotic cells and may cause unwanted loss of some of the membrane components.
The amniotic cell removal method created at Cedars-Sinai takes less than one minute and ensures virtually complete amniotic cell removal and preservation of amniotic membrane components, and also supports the overall growth of various stem and tissue cells.
“We believe that this straightforward and relatively fast procedure would allow easier standardization of amniotic membrane as a valuable stem cell support and improve the current standard of care in corneal stem cell transplantation,” said lead author Alexander Ljubimov, PhD, director of the Eye Program at the Cedars-Sinai Regenerative Medicine Institute. “This new method may provide a better method for researchers, transplant corneal surgeons and manufacturing companies alike.”
Mehrnoosh Saghizadeh Ghiam, PhD, a research scientist in the Regenerative Medicine Institute’s Eye Program, assistant professor in the department of Biomedical Sciences and first author of the study, commented on the potential of the new method.
“The amniotic membrane has many beneficial properties and provides an attractive framework to grow tissue and stem cells for regenerative medicine transplantations, especially in replacing missing stem cells in the cornea,” said Dr. Saghizadeh. “Our method for preparing this scaffold for cell expansion may streamline clinical applications of cell therapies.”
Study: RD/Drug Link Unfounded
In contrast to findings of a recent study, researchers in Denmark did not find an association between use of a class of antibiotics known as fluoroquinolones (such as ciprofloxacin) and an increased risk of retinal detachment, according to a study appearing in the November 27 issue of JAMA.
A recent study found that use of fluoroquinolones was strongly associated with retinal detachment, reporting a 4.5-fold significantly increased risk for ongoing exposure. A possible mechanism was effects of the drug on connective tissue, according to background information in the article: “Given the prevalent use of fluoroquinolones, this could, if confirmed in the general population, translate to many excess cases of retinal detachment that are potentially preventable.”
Bjorn Pasternak, MD, PhD, of the Statens Serum Institut, Copenhagen, and colleagues used data from a nationwide register to investigate whether oral fluoroquinolone use was associated with increased risk of retinal detachment. The register had information about 748,792 episodes of fluoroquinolone use and 5,520,446 control episodes of nonuse, including data on participant characteristics, drugs used and cases of retinal detachment with surgical treatment.
The fluoroquinolones used were ciprofloxacin (88.2 percent), ofloxacin (9.2 percent), fleroxacine (1.2 percent), moxifloxacin (0.8 percent) and others (0.7 percent).
Of 566 patients with retinal detachment, 72 were exposed to fluoroquinolones; five during current use (days one to 10), 7 during recent use (days 11 to 30), 14 during past use (days 31 to 60) and 46 during distant use (two to six months). Among patients not exposed to fluoroquinolones, 494 cases occurred. Analysis of the data indicated that fluoroquinolone use compared with nonuse was not associated with increased risk of retinal detachment.
The authors write that given limited power, the study can only rule out more than a threefold relative increase in the risk of RD associated with current fluoroquinolone use. However, any differences in absolute risk are likely to have limited, if any, clinical significance: In terms of absolute risk, current use of fluoroquinolones would, in the worst-case scenario, account for no more than 11 additional cases of retinal detachment per 1,000,000 treatment episodes. REVIEW