|Department Affiliations||Gastroenterology, Ophthalmology, Cell Biology|
|SOM Address||Room 935 Ross Research Building|
Extracellular matrix of the Cornea In the cornea of the eye, the layer of extracellular matrix (ECM) between the epithelium and the endothelium is the stroma. Rich in collagens and proteoglycans (lumican, keratocan, decorin and others) the corneal stroma is a highly specialized refractive, avascular protective ECM barrier tissue. To understand the role of proteoglycans in the cornea, we developed gene-targeted mice deficient in lumican, a major corneal proteoglycan. Mice deficient in lumican develop abnormally thin corneal stroma with disorganized collagen fibrils and resulting corneal opacity. Lumican also seems to play a major role in regulating immune inflammatory processes in the cornea. To further understand the structure and function of the corneal stroma, we used microarray gene expression profiling to identify novel genes with a strong expression in the corneal stroma. We are currently exploring the possibility of developing gene targeted mouse models deficient in some of these novel corneal proteins to understand their role in the cornea. Extracellular matrix and Inflammatory Bowel Diseases The ECM binds growthfactors, regulates immune responses and provides the environment for inflammatory responses. We are interested in extracellular matrix changes in the pathogenesis of Ulcerative colitis and Crohn’s disease. By microarray gene expression profiling of resected colonic tissue and biopsy tissues obtained during endoscopy to we are beginning to identify differential gene expression patterns associated with these inflammatory diseases. We are now investigating specific ECM and immune/inflammation regulatory genes that are regulated differently in IBD. We have also developed a chemically induced (Trinitrobenzene sulfonic acid treated) mouse model that mimics some of the inflammatory and transmural tissue damage seen in Crohn’s disease, one major form of IBD. Given our interest in the ECM and its role in regulating cellular functions, we are using the mouse model to explore the connection between chronic intestinal inflammation and intestinal fibrosis.
- Chakravarti, S, Magnuson, T., Lass, J. H., LaMantia, C., Jepsen, K. J. and Carroll, H. Collagen fibril defects affecting skin and cornea in lumican-deficient mice. (1998) J. Cell Biol.141: 1277-1286.
- Jepsen, K., Wu, F., Peragallo, J. H. , Paul, J., Roberts, L., Ezura, Y., Oldberg, A., Birk, D. E., Chakravarti, S. A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient mice. (2002) J. Biol.Chem. 277:35532-35540.
- Chakravarti, S., Paul, J., Roberts, L., Oldberg, A., Birk, D. E. Ocular and scleral alterations in gene-targeted lumican-fibromodulin double-null mice (2003) Invest Ophthalmol Vis Sci. 44(6):2422-32
- Lawrance, I. C., Fiocchi , C., Chakravarti, S. Gene expression profiling identifies distinctive disease signatures for ulcerative colitis and Crohn’s disease. (2001) Hum. Molec. Genet. 10:445-456.
- Lawrance, I. C., Wu, F., Leite, A Z.A., Willis , J,.West G. A, Fiocchi C. and Chakravarti, S. A murine model of chronic inflammation-induced intestinal B. (2003) Gastroenterology125: fibrosis down regulated by antisense NF- 1750-1761.
- Vij.N , Roberts. L, Joyce. S and Chakravarti S. Lumican suppresses cell proliferation and aids Fas-Fas ligand mediated apoptosis: implications in the cornea. (2004). (2004). Exp. Eye Res. :78:957-71