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Sally S.
Atherton, Ph.D.
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Regents Professor and Chair, Department of Cellular Biology and Anatomy Joint Professor, Department of Ophthalmology Member and Chair of the Research Centers in Minority Institutions (RCMI) study section; ad hoc reviewer for Visual Sciences A and Visual Sciences C study sections Trustee, Immunology and Microbiology section of the Association for Research in Vision and Ophthalmology (ARVO) Editorial Board, Experimental Eye Research |
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Education and Training:
1970 B.A., Biology, Colby College, Waterville, ME
1973 M.S., Biology, Trinity University, San Antonio, TX
1979 Ph.D., Microbiology, University of Texas Health Science Center, San
Antonio, TX
Postdoctoral Training:
1979-1981 - Molecular
Virology, University of Mississippi Medical Center, Jackson, MS
1981-1984 - Immunology, University of Texas Southwestern Medical School
Research Emphasis:
I am interested in elucidating the immunologic and virologic
mechanisms of ocular virus infections. The overall goal of the studies
in my laboratory is to extrapolate findings from animal models to what
is observed clinically in human patients and in so doing, to be able to
understand the pathogenesis of human ocular diseases. Current projects
require expertise not only in immunology and virology, but also in
neuroanatomy and cell biology, and consequently, projects in my
laboratory employ a variety of cell biology, immunology, virology, and
molecular biology techniques.
There are two primary research projects in my laboratory and
both of these projects are supported by grants from the National Eye
Institute of the National Institutes of Health. Acute retinal necrosis
(ARN) caused by several neurotropic members of the herpes virus family
(HSV-1, HSV-2, VZV) occurs in immunocompetent human patients.
Individuals afflicted with ARN experience acute retinitis which
frequently results in loss of vision in the affected eye. We study a
mouse model of the human disease in which immunocompetent BALB/c mice
are infected intraocularly with HSV-1. Following injection, virus is
transmitted via neuronal routes from the injected eye through the CNS to
the optic nerve and retina of the uninjected eye resulting in acute
retinitis followed by retinal necrosis. We are using the mouse model of
ARN to determine what prevents direct anterior to posterior spread
following infection of the anterior segment, what mechanism prevents
virus that has spread to the brain from infecting the optic nerve of the
virus-infected eye, and the role of T cells and cytokines during virus
infection of the uninoculated eye.
Cytomegalovirus (CMV) retinitis is the most common infectious
ocular complication of AIDS and a significant cause of morbidity and
increased mortality among patients who have received a bone marrow
transplant. The other project in my laboratory uses a model of CMV
retinitis in which immunosuppressed mice are infected with murine CMV (MCMV)
to answer questions about the pathogenesis of CMV retinitis. The aims
of our current project are to define the sites of latency in the eye and
whether the route which is used for ocular infection determines the
sites at which virus will become latent, to determine if MCMV can spread
to and replicate in the retina of immunosuppressed mice following
disruption of the blood-ocular barrier, and to determine the mechanism
by which MCMV infection of the retinal pigment epithelium results in
apoptosis of the overlying retina.
RESEARCH GOALS: The overall goal of our research is to elucidate the
pathogenesis of
herpes virus infections of the eye and brain. A mouse model of herpes
simplex virus type 1 (HSV-1) retinitis is used to study neuronal spread
of virus within the eye and brain, to decipher the components of the
innate and adaptive immune responses that influence the timing and sites
of virus spread and replication during acute infection, and to study the
effect of cytokine-expressing recombinant viruses on the pathogenesis of
CNS and retinal infection. To complement the mouse studies, studies of
human ganglia are used to identify autonomic ganglia in the head and
neck that are sites of herpes virus latency (HSV-1, HSV-2, and VZV).
Cytomegalovirus retinitis is the most common opportunistic ocular
infection in patients with the acquired immune deficiency syndrome. A
mouse model of this disease is used to determine how and when virus
infects the eye, which retinal cells are infected, the role of
macrophages and other effector cells in control of virus spread, and the
sites and timing of virus reactivation in immunologically manipulated
animals.
APPROACHES: To address the above research goals, we use techniques
ranging from the molecular to the whole animal. Techniques used most
frequently are: collection, preparation, and examination of human and
mouse tissues, in vivo immunological manipulation, RT-PCR, TUNEL and
caspase assays, DNA laddering, construction of cytokine-expressing
recombinant viruses, culture of primary cells and of established cell
lines, immunohistochemistry, and confocal microscopy.
FUNDING: National Institutes of Health and unrestricted research funds
RECENT PUBLICATIONS:
Archin NM, van den Boom L, Perelygina L, Hilliard JM, Atherton SS. 2003.
Delayed spread and reduction in virus titer after anterior chamber
inoculation of a recombinant of HSV-1 expressing IL-16. Invest
Ophthalmol Vis Sci. 44:3066-3076.
Zhang, M., Xin, H., Duan, Y., and Atherton, S.S. 2005. Ocular
reactivation of MCMV following immunosuppression of latently infected
BALB/c mice. Invest. Ophthalmol. Vis. Sci. 46:252-258.
Zheng, M. and Atherton, S.S. 2005. Cytokine profiles and inflammatory
cells during HSV-1 induced acute retinal necrosis. Invest. Ophthalmol.
Vis. Sci. 46:1356-1363.
Zhang, M., Xin, H., and Atherton, S.S. Murine cytomegalovirus spreads to
and replicates in the retina after endotoxin disruption of the
blood-retinal barrier of immunosuppressed BALB/c mice. J. Neurovirol.,
In press.
Selected Publications:
Zhao, M. and Atherton, S.S. 1997. Immune effector cell (IEC)-mediated protection from HSV-1 retinitis occurs in the brain. J. Neuroimmunol. 75:51-58.
Matsubara, S. and Atherton, S.S. 1997. T cell depletion correlates with early spread of HSV-1 to the suprachiasmatic nucleus. J. Neuroimmunol. 80:165-171.
Bigger, J.E., Thomas, C.A., and Atherton, S.S. 1998. Natural killer cell modulation of MCMV retinitis. J. Immunol. 160:5826-5831.
Tanigawa, M., Bigger, J.E., Kanter, M.Y., and Atherton, S.S. 2000. Natural killer cells prevent direct anterior-to-posterior spread of herpes simplex virus type 1 in the eye. Invest. Ophthalmol. Vis. Sci. 41:132-137.
Bigger, J.E., Tanigawa, M., Zhang, M., and Atherton, S.S. 2000. Murine cytomegalovirus infection causes apoptosis of uninfected retinal cells. Invest. Ophthalmol. Vis. Sci. 41:2248-2254.