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Bone marrow may restore cells lost in vision diseases

June 09, 2006

UF finding could lead to approaches to treat macular degeneration

GAINESVILLE, Fla.—University of Florida scientists conducting experiments with mice have found evidence that the body naturally replenishes small amounts of cells in the eye essential for healthy vision.

The finding may shatter the belief that a cell layer vital for eyesight called the retinal pigment epithelium, or RPE, is a nonrenewable resource, say researchers writing in a recent issue of Investigative Ophthalmology & Visual Science.

RPE plays a vital role in our visual health by forming the outer barrier of the retina and supporting the function of cells that receive light. Damage to RPE is present in many diseases of the retina, including age-related macular degeneration, which affects more than 1.75 million people in the United States.

With evidence that the body does indeed regenerate these cells in small amounts, scientists can focus on ways to accelerate natural healing processes to treat sight-robbing injuries or diseases.

"What this tells us is for problems such as age-related macular degeneration, we should be able to harvest stem cells to help repair the damage," said senior author Edward Scott, Ph.D., a professor of molecular genetics at the UF Shands Cancer Center and director of the Program in Stem Cell Biology and Regenerative Medicine at UF's College of Medicine. "The question is whether we can do it in a patient."

Scientists widely believe that RPE is a finite resource. The same belief used to be held about brain cells—people who suffered from trauma, stroke or disease formerly faced no hope of growing new cells to replace dead ones.

Then, in the late 1990s, when scientists began to report findings of brain cell growth in humans and monkeys later in life, focus turned toward understanding the mechanisms to regenerate cells in the brain.

Now, UF researchers believe it may be possible to also grow new cells in the retina to replace cells lost to injury or disease.

"In people, retinal pigment epithelium can become damaged with age," said Jeffrey Harris, a graduate student in the department of molecular cell biology in UF's College of Medicine and first author of the paper. "Factors like smoking and diet also come into play. The problem is without these cells, the rods and cones—our primary cells for vision—die. If we can regenerate the retinal pigment epithelium, it could make a big difference in our visual health."

Scientists were able to detect that RPE cells indeed appear to be naturally replenished in the test animals by transplanting bone marrow cells from normal male mice into albino females with two different types of acute RPE injury.

Bone marrow contains stem cells, which have the extraordinary abilities to home in on injuries and possibly regenerate other cell types in the body. In this case, the cells were transplanted to confirm that bone marrow does regenerate the injured RPE. It was easier to track male, pigment-producing cells in female, albino recipients, Harris said.

Chemical and microscopic analysis showed the cells that traveled to the injury site and transformed into RPE indeed had male genetic characteristics. Furthermore, these cells were capable of producing pigment—a colorful indication that the RPE could only have arisen from the donor bone marrow stem cells.

"We did not use a direct model of age-related macular degeneration," Scott said. "But we now know that when RPE is injured, it can be replaced in certain situations. It gives us growth factors, cell pathways and other different places to look at to find reasons why the disease is occurring."

Researchers want to discover ways to mobilize an elderly patient's own cells to travel to the injury site to make repairs.

"The dogma has been that we're born with a fixed amount of RPE, but there is growing evidence retinal progenitor cells exist in the adult," said Lawrence Rizzolo, Ph.D., a Yale University associate professor of anatomy and experimental surgery and of ophthalmology and visual science who was not involved in the research. "To derive cells of neuronal lineage from cells of bone-marrow lineage is significant, if the finding stands up to the test of time. Compared to RPE transplantation, there are a lot of advantages if someone's own bone marrow could supply the cells, because it's a ready source and the cells would not be rejected by the patient. Further, if bone-marrow progenitors circulating in the blood could be attracted to sites of disease, surgery could be avoided."

University of Florida