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Researchers discover mechanism that may enable stem cell-based treatment for eye disorders


UCI study shows how newly identified signaling protein helps control retinal development

In discovering a protein that helps organize the development of the retina, UC Irvine researchers have found a new molecular mechanism that may allow for stem cell-based therapies to treat eye disorders such as retinal degeneration.

The finding also reveals how the retina’s own stem cells can be directed to aid the growth of new cells to replace diseased or dying ones in the eye. Study results appear in the June 24 issue of the journal Science.

Anne L. Calof in the Department of Anatomy and Neurobiology and her UCI colleagues have identified how a protein called GDF11 controls a key component of retinal-cell differentiation during development, which makes GDDF11 an attractive therapeutic target.

"By manipulating the ability of this protein to control cell development, there is the potential for therapeutics to harness the power of the stem cells that already exist in the retina to replace any retinal cells that have been lost or injured," Calof said. "If so, we thereby may be able to cure visual disorders that result from loss of certain retinal cell types."

During the process of embryonic development, groups of neural precursor cells, which are formed from stem cells, are given brief periods of time to differentiate into their specific tissue forms, a process that is tightly regulated by signaling proteins.

In tests on developing mice, the Calof group observed that the GDF11 protein precisely controls the "window of opportunity" in which retinal precursor cells differentiate into the cells that give rise to the optic nerve. This regulation is important, Calof said, because it assures proper development of the entire retina, a nerve cell layer that lines the back of the eye, senses light and creates the electrical impulses that travel through the optic nerve to the brain.

GDF11 is part of the superfamily of TGF-beta proteins, which are widely studied for their role both in human development and in diseases like cancer. Because the structure and properties of these proteins are well known, GDF11 is an especially attractive target for potential drug treatments.

Therapies based on this protein become possible, Calof said, because the retina contains its own stem cells, which among other things, generate the photoreceptors that allow us to see color. However, harvesting these cells for therapeutic purposes may not be feasible. While researchers have created ways to extract adult stem cells from the body, the process is difficult and rarely successful.

Rather than removing adult stem cells and reintroducing cultured ones into the eye, Calof said, a drug therapy based on the GDF11 protein may be able to harness the power of these endogenous stem cells by directing the differentiation of these cells into specific retinal cell types.

"The ultimate goal is to control how GDF11 and related proteins regulate the window of opportunity for neural cell growth," Calof said. "If we or other researchers can accomplish this, we will come one step closer to understanding how to manipulate neural stem cells for therapeutic good."

The research was supported by the National Institutes of Health and the March of Dimes Birth Defects Foundation. Joon Kim, Hsiao-Huei Wu and Arthur Lander of UCI, along with Karen Lyons of UCLA and Martin M. Matzuk of Baylor College of Medicine, participated in the study. UCI has filed a patent for use of GDF11 and related proteins and antagonists in treatment of retinal disorders.

Tom Vasich | EurekAlert!
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