Aging is a gradual process. During this process cumulative damage to long-lived connective tissue proteins such as collagen, elastin, and lens crystallins occurs. Our efforts are directed toward understanding the mechanisms through which such damage is incurred and how it contributes to age-related disease. Specifically, we have developed an in vitro model system used to study age-related connective tissue protein damage caused by reaction with nitrite ion. Nitrite is a biologically relevant compound because augmented human exposure can result from cigarette smoking, inflammation, and dietary cured meat ingestion.
In recent studies we have shown that nitrite induced basement membrane protein damage can impart deleterious effects on overlying retinal pigment epithelial cells, a key step in the development of Age-related Macular Degeneration. We have also shown that nitrite induced cross-linking of fibrillar collagen can result in tissue stiffening, a process implicated in many age-related diseases.
The potential implications of this research program are vast, since age-related connective tissue protein damage is found throughout the human body. Future and ongoing studies will be directed toward better understanding the role of these reactions in age-related diseases as well as developing modalities capable of preventing, retarding, and/or reversing such aging changes.
Finally, although we believe that these reactions likely play a deleterious role in the development of age-related diseases, such reactions may also have a therapeutic application. Collagen stabilization through cross-linking (using UV/riboflavin) is an emerging technology for the treatment of corneal conditions such as keratoconus in which progressive slippage of collagen lamella occurs. In this regard, we are evaluating the utility of nitrite induced collagen cross-linking as an alternative therapeutic technology for corneal stabilization.
Major Collaborators:
Dr. Elizabeth R. Gaillard Department of Chemistry Northern Illinois University
Dr. James P. Dillon Department of Ophthalmology Columbia University
Dr. Jeffrey W. Holmes Department of Biomedical Engineering Columbia University
Dr. Lucian V. Del Priore - Department of Ophthalmology Columbia University
Dr. Stephen L. Trokel - Department of Ophthalmology Columbia University
Dr. R. Graham Barr Department of Medicine Columbia University
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