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Results with research

When they’re not seeing patients or teaching tomorrow’s ophthalmologists, our faculty members are involved in research aimed at reducing the impact eye diseases and disorders will have on future generations. Here are a few highlights of their current research.

Deborah Ferrington, Ph.D. (standing), with former graduate student Cheryl Ethen, is investigating the role of proteins in retinal diseases.

Deborah A. Ferrington, Ph.D. Associate professor

Ferrington and her colleagues are investigating the role proteins play in indicating diseases of the retina such as macular degeneration and diabetic neuropathy.

The retina is the part of the eye that captures light rays and turns them into electrical impulses, which are then converted into the images we see.

“Research involving the retina is very challenging and very intricate,” Ferrington says. “It’s my hope that the research we’re conducting in the lab may someday prove helpful in treating human diseases involving the retina.”

Knowing that the way proteins change in the diseased retina could provide insight into the disease process, Ferrington and her colleagues developed a novel technique to analyze 500 to 1,000 proteins simultaneously.

Ferrington has found that parts of the retina that have been previously ignored are, in fact, sensing disease before it can be detected by doctors. Her laboratory conducted a study with donor eyes from people who had diabetes but who had not yet exhibited symptoms of diabetic retinopathy, a complication of diabetes and a leading cause of blindness in American adults. An analysis of the proteins present in the retinas from these diabetic donors showed that they were indeed changed, even though the disease was not advanced enough to be diagnosed.

Ferrington’s laboratory works in conjunction with another laboratory in the department. Her colleague Timothy Olsen, M.D., created a unique system for grading tissue from donor eyes, assigning one of four levels—from no macular degeneration present to end-stage macular degeneration, in which case the patient would have been legally blind. The system is identical to the one used for grading living patients’ eye tissue.

“This has never been done before, and it means that the protein analysis done in our laboratory applies directly to living patients,” says Ferrington.

Alana Grajewski, M.D. Professor

Glaucoma, a disorder that damages the optic nerve and can lead to blindness, affects children as well as adults. An estimated 1 in 25,000 infants in the United States is born with glaucoma.

If surgery is performed to correct the problem right away, there is a 90 percent to 95 percent chance the child will develop normal vision.Without surgery, the child may become blind.

It is this ability to “make a profound difference in the life of a child—the difference between sight and blindness” —that makes treating pediatric glaucoma such a passion of Grajewski’s.

Her research focuses on the genetics of pediatric glaucoma and on the most effective treatment for children. “It’s terribly important to make the diagnosis early enough and to treat the child, because once the optic nerve is damaged, vision can’t be recovered,” says Grajewski. “We need to ask if we’re diagnosing and treating these children early enough and how effective the treatments are.”

A diagnosis can be made in utero through amniotic testing, and Grajewski has operated on premature babies before they are full gestational age. In African American and African Caribbean children, a slightly different type of pediatric glaucoma occurs and is usually treated first with drops, then with surgery.

Grajewski is working to establish a new Center for Pediatric Glaucoma at the University.With data gathered here and at a similar center at the Bascom Palmer Eye Institute at the University of Miami, Grajewski will have access to a large pool of patient information needed to make meaningful conclusions about the best way to treat pediatric glaucoma.

“This will be a team effort,” she says. “I’m going to need to surround myself with people who are good at epidemiology to help me answer the big questions about how we identify and treat this patient population.”

Linda McLoon, Ph.D., and Michael Lee, M.D., are experimenting with intranasal delivery of medication directly to an injured optic nerve.

Michael S. Lee, M.D. Associate professor Linda McLoon, Ph.D. Professor

Anterior ischemic optic neuropathy, the most common optic nerve disorder in patients over age 50, causes vision loss and has no cure or effective treatment. It typically comes on suddenly. Vision worsens in about 30 percent of people with the disorder, and 15 percent will eventually develop the condition in both eyes.

While relatively rare—affecting only 5 in 100,000 people—” it can be a devastating condition when it occurs,” says Lee. Anterior ischemic optic neuropathy affects the eye’s optic nerve, a cable that transmits visual information from the eye to the brain.

“Most people who get the condition have a small optic nerve, which is thought to be a predisposing factor, but there are thousands of people with a small optic nerve who don’t get neuropathy,” Lee says. “Something happens—we don’t know what—and swelling of the optic nerve occurs. Because the canal that holds the nerve is small, the swelling compresses the nerve against the walls of that canal.”

Lee and McLoon, a laboratory scientist, are in the early stages of experimenting with delivering medication through the nose to patients with neuropathy. They hope nose drops will be an effective way to deliver sufficient doses of the medication directly to the retina and injured optic nerve.

Delivering the medication any other way requires large doses because of the blood-brain barrier and may cause negative side effects. Smaller doses of medication likely wouldn’t be optimally effective.

“Even though we’re far from applying this treatment to patients, it’s reasonable to think that patients could administer these nose drops on their own someday,” McLoon says. “It will be interesting to see what this research uncovers. Sometimes the simplest approach turns out to be the most effective one.”

Stephen P. Christiansen, M.D. Professor

Strabismus, or misalignment of the eyes, is a condition that ophthalmologists treat frequently, usually with surgery.

Christiansen is working with McLoon to develop new medications to treat the condition that could either weaken or strengthen the eye muscles to help realign the eyes. “If further testing shows that these drugs can be used safely in humans, that would mean significant changes in the way we treat children and adults who have strabismus,” says Christiansen. “The treatment will be shorter, and we hope it will have longer-term success rates than current treatments.”

And in conjunction with the neonatology and nursing staff at the University of Minnesota Medical Center, Fairview, Christiansen is also conducting research on a condition in newborn babies called retinopathy of prematurity (ROP). Common in premature infants, ROP is an eye disorder that occurs when abnormal blood vessels grow and spread above the retina, causing it to detach. In the most severe cases, the child may become blind.

Every year, approximately 1,100 to 1,500 infants in the United States develop ROP that is severe enough to require medical treatment.

In the past, standard use of oxygen to help premature babies stay healthy also stimulated the growth of abnormal blood vessels in the eye. Today, by lowering oxygen saturation levels for premature infants in hospitals’ neonatal intensive care units, Christiansen says doctors are seeing dramatically lower rates of severe ROP.

After oxygen saturation levels were lowered at the University of Minnesota Children’s Hospital, Fairview, for instance, the number of premature infants who developed severe retinopathy decreased from 28 percent in 2005 to 14 percent in 2006. There was also a 50 percent reduction in the number of infants requiring surgery to correct the disorder.

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