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Catherine Bowes Rickman, Ph.D.
Assistant
Professor, Ophthalmology
Assistant Professor, Cell Biology
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The macula is a unique and highly specialized
region of the retina with anatomic and functional properties
enabling high acuity vision (color, sharpness, and clarity).
The unique anatomic structure of the macula, compared
to peripheral retina, includes a greater overall density
of photoreceptors, the highest density of cone photoreceptors
(at its center known as the fovea), underlying neural
circuitry and increased metabolic rate. Unfortunately,
loss of central vision is a significant consequence of
various retinal degenerations, including cone-rod dystrophies
and macular degenerations (such as age-related macular
degeneration or AMD). The long-term goal of this research
program is to understand fundamental processes of foveal
cone photoreceptor biology and their alterations in degenerative
disease processes. To better understand these cells, other
unique features of the macula and their potential involvement
in macular degeneration and dystrophies we have isolated
fovea-associated genes. Genes with increased expression
in the fovea compared to peripheral retina might be involved
in retinal development, cone photoreceptor biology, or
maintenance of macular function. Ultimately, these studies
will provide the rationale for therapies to prolong photoreceptor
survival in macular degenerations.
We have developed a method for identifying
genes enriched in the primate fovea from human donor retinas.
RNA transcripts enriched in foveal cones are isolated
by 'subtracting' them from transcripts derived from the
peripheral retina. Fovea-associated genes are also being
identified by differential screening of custom high-density
cDNA macroarrays, and commercial microarrays. The molecular
characteristics and distribution of human fovea-associated
cDNA clones are determined by DNA sequence analyses, chromosomal
mapping, in situ hybridization and immunocytochemistry.
Biochemical studies of several of the
protein products of the fovea-associated genes identified
are also underway. One foveal cone-associated gene identified
from this library is PRL-1, which codes for a protein
tyrosine phosphatase specifically localized to the outer
segments of red and green - but not blue - cone photoreceptors
in the retina. PRL-1 maps within the genetic interval
of an autosomal dominant cone-rod dystrophy known as CORD7.
Another gene, FASH3B, maps within the interval for STGD3
(Stargardt-like dominant progressive macular dystrophy)
and codes for a novel small protein of unknown function
that contains an SH3 binding motif and is expressed in
the cone photoreceptors.
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Email
bowes007@duke.edu
353B Sands Bldg, Box 3802
Duke University Medical Center
Durham, NC 27710
Telephone 919-668-0648
Lab phone 919-668-0649
Fax 919-684-3687 |
Selected
Publications
Bowes,C., Danciger, M., Kozak, C.A., and Farber, D.B.
(1989) Isoaltion of a candidate cDNA for the gene causing
retinal degeneration in the rd mouse. Proc. Natl. Acad.
Sci., USA 86: 9722-9726.
Danciger, M., Bowes, C., Kozak, C.A., LaVail, M.M. and
Farber, D.B. ( 1990) Fine mapping of a putative rd cDNA
and its cosegregation with rd expression. Invest. Ophthalmol.
Vis. Sci. 31: 1427-1432.
Bowes, C., Li, T., Danciger, M., Baxter, L.C., Applebury,
M.L. and Farber, D.B. (1990) Retinal degeneration in the
rd mouse is caused by a defect in the b subunit of rod
cGMP-phosphodiesterase. Nature 347: 677-680.
Klumpp, D.J., Farber, D.B., Bowes, C., Song, E.-J. and
Pinto, L.H. (1991) The potassium channel MBK1 is expressed
in the mouse retina. Cell Mol. Neurobiol. 11: 611-622.
Farber, D.B., Bowes,C. and Danciger, M.D. (1991) Studies
leading to the isolation of a cDNA for the gene causing
retinal degernation in the rd mouse. In "Progress
in Clinical and Biological Research", Farber, D.B.
and Chader, G.J., eds, Wiley-Liss, Inc., New York, vol.
362, pp 67-86.
Farber, D.B., Danciger, M., and Bowes, C. (1991) Studies
on the gene defect of the rd mouse. In "Retinal Degenerations",
Anderson, R.E., Hollyfield, J.G., and LaVail, M.M., eds.,
CRC Press, pp 445-454.
Bateman, J.B., Klisak, I., Kojis, T., Mohandas, T., Sparkes,
R.S., Li, T., Applebury, M.L., Bowes, C., and Farber,
D.B. (1992) Assignment of the b subunit of rod photoreceptor
cGMP phosphodiesterase gene, PDEB (Homolog of the mouse
rd gene) to human 4p16. Genomics 12: 601-603.
Bowes,C., Li, T., Frankel, W.N., Danciger, M., Coffin,
J.M., Applebury, M.L., and Farber, D.B. (1993) Localization
of a retroviral element within the rd gene coding for
the b subunit of cGMP phosdiesterase. Proc. Natl. Acad.
Sci., USA 90: 2955-2959.
Farber, D.B., Flannery, J.G., and Bowes-Rickman, C. (1994)
The rd mouse story: Seventy years of research on an animal
nodel of inherited retinal degeneration. In "Progress
in Retinal Research", Osborne, N. and Chader, G.J.,
eds., Vol.13, 31-64.
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Kozak,
C.A., Danciger, M., Bowes, C., Adamson, M.C. Palczewski,
K., Polans, A.S., and Farber, D.B. (1995) Localization
of Three Genes Expressed in the Retina on Mouse Chromosome
11. Mammalian Genome 6:142-144.
DiPolo, A., Bowes Rickman, C., and Farber, D.B. (1996)
Isolation and Initial Characterization of the 5’
Flanking Region of the Human and Murine cGMP Phoshodiesterase
the b subunit Genes. Invest. Ophthal. Vis. Sci. 37:551-560.
Rickman, D.W. and Bowes Rickman, C. (1996) Suppression
of trkB by Antisense Oligonucleotides Alters a Neuronal
Phenotype in the Rod Pathway of the Developing Rat Retina.
Proc, Natl. Acad. Sci. USA 93:12564-12569.
Rickman, D.W., Nacke, R.E. and Bowes Rickman, C. (1999)
Characterization of the Cell Death Promoter, Bad, in the
Developing Rat Retina and Forebrain. Dev. Brain Res. 115
(1): 41-47.
Yarovinsky, T.O., Rickman, D.W., Diamond, R.H., Taub,
R.,
Hageman, G.S. and Bowes Rickman, C. (2000) Expression
of the Protein Tyrosine Phosphatase, Phosphatase of Regenerating
Liver 1, in the Outer Segments of Primate Cones. Mol.
Brain Res. 77 (1): 95-103.
Johnson, J., Bowes Rickman, C., Rickman, D.W. and Brecha,
N.C. (2001) A Receptor for Somatostatin is Expressed by
Cone Photoreceptors in the Primate Retina. Vis. Neurosci.
(in press).
Kuehn, M., Warner, R., Bowes Rickman, C. and Hageman,
G.S. (2001) Differential Expression of Genes in Retinal
Pigmented Epithelial Cells Derived from Human Donors with
Age-Related Macular Degeneration. J. Clin. Invest. (submitted).
Bowes Rickman, C., Ritter, R. Yarovinsky, T.O., McKay,
B.S., Stone, E.M., Donoso, L.A., Rickman, D.W. and Edwards,
A.O. (2001) Characterization of a novel fovea-associated
gene, FASH3B, expressed in cones and localized to the
chromosome 6q retinopathies region. (Submitted) |
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