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Office: 803 733 3293
Fax: 803 733 3192
E-mail:
mhunt
@med.sc.edu
Department of Pathology, Microbiology
and Immunology, University of South Carolina School of Medicine, Columbia, SC
29208
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Dr. Hunt's current research focuses on
the retinal pigment epithelial (RPE) cells of the eye. These cells support
the nutrition of photoreceptor cells and remove the shed photoreceptor
membranes that are produced on a diurnal basis. Any malfunction of the RPE
cells leads to atrophy of the photoreceptor cells and blindness. Among the
human diseases that may result from changes in the pigment epithelium are
age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR).
PVR is a major blinding disease that can occur spontaneously but often
results from trauma to the retina. The RPE cells transform from a quiescent
columnar epithelial phenotype to motile fibroblast-like cells that
proliferate and invade the matrix of the vitreous. This process of
epithelial-mesenchymal transformation (EMT) is similar to the EMT that
occurs in the formation of neoplastic cells. Normally, the apical surface of
the RPE cells is separated from the vitreous by the neural retina but after
a tear in the retina, collagen and numerous growth factors in the vitreous
can bind to receptors on the RPE cells. It is thought that this leads to the
altered behavior of the cells, and risk factors implicate contact of the
vitreous with the surface of RPE cells as important in the transformation
process.
When human RPE cells are grown in culture in the presence of vitreous, they
undergo a similar transformation to that seen in PVR in vivo. Again,
there are changes the shape, proliferation, motility and invasiveness of the
cells and this is accompanied by altered gene expression. Current research
involves the elucidation of the gene expression changes that occur when
cultured RPE cells transform since knowledge of the pathways that are up-
and down- regulated will tell us how vitreous causes the changes in the
cell’s phenotype. Using gene array analyses, we have identified several
hundred genes that exhibit altered expression and have identified some of
the signaling pathways involved in cellular transformation; among those of
particular interest are the transforming growth factor-beta and bone
morphogenetic protein-2 pathways. We are now studying how these and other
pathways lead to cellular transformation. |
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