View Annual Report - Jules Stein Eye Institute

Gabriel h. Travis, mD
Charles Kenneth Feldman Professor of Ophthalmology
Associate Director of the Jules Stein Eye Institute
Co-Chief of the Vision Science Division
ReseaRch summaRy
Biochemistry of Vertebrate
Photoreceptors and Mechanisms
of Retinal Degeneration
Dr. Travis’ laboratory uses biochemical and genetic
approaches to study the visual cycle and its role in
retinal and macular degenerations. Vision in vertebrates
is mediated by two types of light-sensitive cells: rods
and cones. These cells contain light-detecting molecules
called opsin pigments. Detection of a single light
particle bleaches the opsin pigment. Restoring light
sensitivity to a bleached opsin involves an enzymatic
pathway called the visual cycle. Mutations in the genes
for many proteins of the visual cycle cause inherited
blinding diseases.
One project in Dr. Travis’ laboratory studies the function
of a transporter protein in rods and cones called ABCA4.
Mutations in the human ABCA4 gene cause recessive
Stargardt macular degeneration and cone-rod dystrophy.
Dr. Travis’ group generated mice with a null mutation in
this gene. Biochemical analysis of the phenotype in these
ABCA4 “knockout” mice led them to the function of
ABCA4 in photoreceptors, and the biochemical etiology
of Stargardt disease. This understanding suggested a
pharmacological strategy to reverse the biochemical
defect in patients with Stargardt disease and agerelated
macular degeneration. A phase II clinical trial is
currently underway to test a drug based on this strategy
as a treatment for age-related macular degeneration.
Another ongoing project in Dr. Travis’ laboratory characterizes
Rpe65, which catalyzes the critical isomeriza-
tion step in the visual cycle. Previously, Dr. Travis and
co-workers identified Rpe65 as the retinoid isomerase.
Still another project in Dr. Travis’ laboratory concerns
the mechanism of visual-pigment regeneration in cone
photoreceptors. Despite the importance of cones, little
is known about how visual pigments are replenished
to permit sustained vision under daylight conditions.
Recent results from Dr. Travis’ group point to the
existence of a new enzymatic pathway for regenerating
visual pigments in cones. His group is currently working
to purify and clone the enzymes that define this new
biochemical pathway.
Public Service
Scientific Advisory Panel Member, the Karl Kirchgessner
Foundation Vision Science Program
Grant Reviewer, National Institutes of Health:
The Biology and Diseases of the Posterior Eye
Study Section
Reviewer, Howard Hughes Medical Institute Investigators
Reviewer for many scientific journals
Research Grants
California Institute for Regenerative Medicine:
Development of a Stem Cell-Based Transplantation Strategy
for Treating Age-Related Macular Degeneration
(Principal Investigator, with other investigators),
11/1/09–10/31/12
National Eye Institute: The Role of Muller Cells in
Visual Pigment Regeneration, 3/1/08–2/28/13
National Eye Institute: Vision Science Training Grant
for the Jules Stein Eye Institute (Principal Investigator),
9/30/05–9/29/12
Bruce Ford and Anne Smith Bundy Foundation,
8/16/11–8/15/12
Faculty | Travis 63