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Jeanne M. Frederick, Ph.D.
Identification of genes involved in inherited
human retinal disorders is the goal of
research conducted by Jeanne Frederick,
Ph.D. and Wolfgang Baehr, Ph.D. One of
the best known heritable retinal diseases
is retinitis pigmentosa (RP). Multiple genetic
causes, each identified at the molecular
level, are responsible for RP. The
general approach to this research is twofold:
to understand the molecular mechanism
responsible for degeneration, and
to design rational strategies to intervene
and, eventually, retard or reverse disease
onset. One method involves development
of an animal strain that mimics a human
disease. For example, knowing a specific
DNA alteration in human visual pigment
that is associated with RP, the same alteration
can produce a comparable retinal
degeneration in mice which can then be
used to study the physiology, biochemistry
and morphology of the retina.
Naturally occurring animal models with outer retina phenotypes.
Baehr W, Frederick JM.
Journal: Vision Res. 2009 Nov;49(22):2636-52. Epub 2009 Apr 16.
ABSTRACT: Naturally occurring and laboratory generated animal models serve as powerful
tools with which to investigate the etiology of human retinal degeenerations, especially
retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone dystrophies (CD) and
macular degeneration (MD). Much progress has been made in elucidating gene defects
underlying disease, in understanding mechanisms leading to disease, and in designing molecules
for translational research and gene-based therapy to interfere with the progression of
disease. Key to this progress has been study of naturally occurring murine and canine retinal
degeneration mutants. This article will review the history, phenoteypes and gene defects
of select animal models with outer retina (photoreceptor and retinal pigment epithelium)
degeneration phenotypes.
Trafficking of Membrane Proteins to Cone but not Rod Outer Segments is Dependent
on Heterotrimeric Kinesin-II
Avasthi P, Watt CB, Williams DS, Le YZ, Li S, Chen CK, Marc RE, Frederick JM, Baehr W.
Journal: J Neurosci. 2009 No 11;29(45):14287-98.
SUMMARY: Heterotrimeric Kinesin-II is a molecular motor localized to the inner segment,
connecting cilium and axoneme of mammalian photoreceptors. Our purpose was to identify
the role of kinesin-II in anterograde intraflagellar transport (IFT) by photoreceptor-specific
deletions of KIF3A, its obligatory motor subunit. In cones lacking KIF3A, membrane proteins
involved in phototransduction did not traffic to the outer segments resulting in complete
absence of a photopic electroretinogram and progressive cone degeneration. Rod photoreceptors
lacking KIF3A degenerated rapidly between two and four weeks postnatal, but
the phototransduction components including rhodopsin trafficked to the outer segments during
the course of degeneration. Further, KIF3A deletion did not affect synaptic anterograde
trafficking. The results indicate that trafficking of membrane proteins to the outer segment
is dependent on kinesin-II in cone, but not rod photoreceptors, even though rods and cones
share similar structures, and closely related photo transduction polypeptides.
Jun Yang, Ph.D.
Dr Yang’s laboratory is focused on the disease mechanisms and therapeutic treatments for
retinal degenerative diseases using mouse models. Her research group investigates the biological
functions of genes whose mutations are known to cause human retinal disease. Using
mouse models for these diseases, the group also studies treatment of these diseases by means
of gene therapy. Dr.Yang’s team is also interested in the cell biology of photoreceptors, especially
the cellular processes of intracellular trafficking, structural maintenance, and calcium
regulation.