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Scientist Lands $1.7 Million NIH Grant for Tissue Engineering Approach

From left: Marc Kantorow, Ph.D., principal investigator, a professor of biomedical science, and assistant dean for graduate programs, and Lisa Ann Brennan, Ph.D., collaborator on the project and a research associate professor, 91����’s Schmidt College of Medicine. (Photo by Alex Dolce)

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The prevalence of eye disease in the United States is staggering, despite major advances in treatment options and surgeries. According to the National Eye Institute, 2.1 million Americans have age-related macular degeneration, 2.7 million have glaucoma, and 24 million have cataracts. By 2030, 34 million Americans will have cataracts, and worldwide, it is the leading cause of blindness.

To help combat these debilitating conditions and gain insight to advance regenerative medicine, researchers from 91����’s have received a five-year R01 grant totaling $1,738,565 from the National Eye Institute of the National Institutes of Health (NIH) for a novel project titled “Hypoxia Regulation of the Lens.” The project is focused on identifying the role of hypoxia or lack of oxygen to the cells and tissues in the body, and oxygen on the formation of the eye lens.

“The promise of regenerative medicine depends on our ability to engineer transplantable tissues that can replace diseased or damaged tissues,” said , Ph.D., principal investigator, a professor of biomedical science, and assistant dean for graduate programs in 91����’s Schmidt College of Medicine. “Although many studies have identified a wide-range of factors that can induce stem cells to differentiate into immature cells, these engineered cells often do not attain the structure and mature cellular characteristics needed for them to carry out their normal functions.”

Kantorow and his team have identified hypoxia and oxygen regulation as a novel requirement for newly made lens cells to achieve their mature cellular structure and transparent visual function. They are working to identify the molecules and cellular pathways required for this critical cellular transformation. The information they gain from these studies will be applicable toward the development of novel tissue engineering strategies to develop ocular and other cells for replacement of damaged and diseased tissues.

During embryogenesis and throughout life, lens epithelial cells continuously differentiate into lens fiber cells that make up the core and bulk of the lens. To achieve their mature structure and transparent function, newly-formed lens fiber cells must complete a precise program of cellular remodeling hallmarked by the complete elimination of organelles and the tightly controlled expression of specialized proteins.Disruption of the lens fiber cell remodeling program results in loss of lens structure and cataract formation. Therefore, identification of novel lens fiber cell remodeling mechanisms and regulatory pathways is critical toward establishing the requirements for mature lens formation and lens pathology.

“Our research and analysis of these mechanisms and regulatory pathways in the eye lens could also advance our understanding of the cellular remodeling requirements that are important for the formation and function of more complex tissues,” said , Ph.D., collaborator on the project and a research associate professor at 91����’s Schmidt College of Medicine.

The focuses on understanding mitochondrial mechanisms in ocular development and disease. Specifically, his team focuses on the eye lens and the retina as models for understanding cell differentiation, cell function and disease. Their work ranges from analysis of the functions of genes identified to cause ocular disease when mutated, to the direct effects of UV-light and other agents associated with the development of ocular disease on mitochondrial and other cell functions.

In addition to understanding how the functions of ocular cells are altered in disease states, the Kantorow Laboratory team examines how manipulation of key cell systems can be applied to treat and/or prevent ocular diseases including age-related cataract formation and macular degeneration that are the leading causes of visual disability. Knowledge gained from these studies to engineer cell systems and cells that can be transplanted into cells or tissues could restore the functions of damaged organs.

“This significant NIH grant awarded to Dr. Kantorow and his team could provide important insights into the development of novel therapies to prevent and treat cataracts, which impact people globally,” said , Ph.D., senior associate dean for research and chair of the Department of Biomedical Science in 91����’s Schmidt College of Medicine. “Furthermore, the information gained from their research will provide an understanding into how disruption of the cellular remodeling events required for the form and function of more complex tissues could also lead to pathologies of these tissues.”

The Kantorow Laboratory and research program have been continually funded by the NIH’s National Eye Institute for almost two decades.

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