AABRE: NETWORKING IN PUERTO RICO
PR-AABRE Researcher: Karen González, Ph. D., Department of Sciences and Technology, Universidad Metropolitana
Cluster: Molecular Medicine
Collaborator: Larry Takemoto, Ph.D. (Kansas State University)
Mentor: José R. Rodríguez-Medina, Ph.D. (UPR, Medical Sciences Campus)
Project Title: Cell Cycle Changes in the Galactosemic Lens
WHEN THE BODY IS EXPOSED to high concentrations of sugars, as in diabetes, one of two complications can occur in the eyes: diabetic retinopaphy, which results from damage to the capillaries in the retina and is the leading cause of blindness in people ages 20 to 74, or cataract formation.
A cataract is a clouding of the eye’s crystalline lens, which is a clear tissue located behind the pupil. The lens works with the transparent cornea, which covers the eye’s surface, to focus light on the retina at the back of the eye. But when the lens becomes cloudy, light cannot pass to the retina properly and vision is blurred. Researchers know that diabetics who don’t control their sugar intake are at a risk of developing cataracts, but they don’t understand the mechanism that causes the cataracts to develop.
Biologist and Dean of the School of Science and Technology at Universidad Metropolitana, Karen González, is looking at sugar cataract formation from the cellular point of view. She and her team of student researchers along with Larry Takemoto, Ph.D., professor of biology at Kansas State University and president of the Association for Research in Vision and Ophthalmology, are studying the epithelial layer, the layer of cells in front of the lens and the only layer growing within the lens, to prove her hypothesis: exposure to galactose causes changes in the cell cycle. Dr. José Rodríguez-Medina from the Department of Biochemistry at the Medical Sciences Campus of UPR, an expert in cell cycles, is a collaborator in this project.
The cell cycle includes four phases: 1) the G1 Phase, in which cells grow in size; 2) the S Phase (S stands for synthesis), in which cells manufacture DNA and duplicate their genetic material; 3) the G2 Phase, the second growth phase and preparation phase for the cell; and 4) the M Phase, or mitosis and cytokinesis, in which the cell divides into two daughter cells. During the cycle, a surveillance system, a series of checkpoints, monitors the cell for DNA damage and failure to perform critical processes. Checkpoints can block progression through the phases of the cell cycle if certain conditions are not met.
“When the cells are insulted by galactose, a type of sugar found in dairy products or synthesized by the body, they react by halting cell cycle progression in one of the cell cycle checkpoints. Once the cells are exposed to sugar, there is a series of biochemical changes—a chain of reactions,” González says.
Previously, researchers had used rat lens cells to investigate sugar cataracts, but biochemically they are very different from human lens cells. González’ team experiments with bovine epithelial lens cells in vitro because they are morphologically and biochemically similar to human epithelial lens cells. Their research has revealed that bovine lens cells exposed to high galactose increase their rate of mitosis for four days, but by day seven the rate of mitosis decreases dramatically, as compared to control cells.
The researchers hope to demonstrate that changes in cell progression in the sugar-exposed cells are a consequence of the activation of a checkpoint at the G2–to–mitosis transition. The changes will be measured using several techniques, including Western blot analysis of the cyclin-dependent kinases that may be involved in the process, kinase activity assays, and cell–cycle profile analysis using flow cytometry.
Although cataract surgery in which the cloudy lens is replaced with an artificial lens is common, it is expensive and costs the government millions of dollars annually because Medicare covers it, says González. In addition, like all surgery, it involves risks, including somatic rejection of the lens and the creation of scar tissue.
An estimated ten percent of Puerto Rican adults have diagnosed diabetes, about twice that of non-Hispanic whites. Therefore, this research is particularly important to Puerto Rico.
“NIH’s philosophy is that it is better to prevent diseases than to treat them. Our research aims to understand the mechanism by which diabetic cataracts form in order to develop better preventative measures.” um_kgonzalez@suagm.edu
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