a new large animal model for studying and testing treatments of angioproliferative eye diseases
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Editor’s Choice
Mathematical modellingelucidates sex disparities inhuman cardiac physiology
�Sex differences in ICa,L, Ito and IKrdensities may explain sex disparities in
human cardiac electrophysiology�.
Sex disparities in human physiology
include defined gender-related differ-
ences in cardiac physiology and patho-
physiology. Among the mammalian
gender dependent disparities are the
differences in the cardiomyocyte ion-
channel densities; cardiomyocytes
from female hearts generally have a
higher density of depolarizing calcium
current and a lower density of repo-
larizing potassium currents than males.
These differences may explain the
characteristic sex dependent differ-
ences in electrocardiogram (ECG)
variables, heart rate and susceptibility
to certain types of arrhythmias. Ver-
kerk et al. (Amsterdam, the Nether-
lands) have studied these sex
disparities at the cellular electrophysi-
ology level with mathematical model
simulations. They have implemented
known gender-related differences in
ion-current densities into human ven-
tricular cell mathematical models to
simulate ventricular action potentials
and ion currents. The authors predict
with simulations that female cells have
a longer action potential duration
(APD), steeper APD–heart rate rela-
tionship and larger transmural APD
heterogeneity, which together increase
the susceptibility of female myocytes
to arrhythmogenic early afterpoten-
tials. On the other hand, male myo-
cytes having faster repolarization are
more susceptible to all-or-none repo-
larization. This study suggests that
part of the sex disparities in cardiac
physiology can result from endogenous
differences in cardiomyocyte ion-
channel densities between females and
males.
Pasi TaviDepartment of Physiology,University of Oulu, Oulu,
Guest editor
A new large animal model forstudying and testing treatmentsof angioproliferative eyediseases
�Intravitreal overexpression of
VEGF-A (vascular endothelial growth
factor-A) using an adenoviral vector
caused a dose-dependent neovessel
formation in the rabbit eye. This
model gives us new possibilities for the
development of gene therapy and other
new treatments for ocular tissues�.
Excessive angiogenesis is a major
problem in many ocular diseases, such
as diabetic proliferative retinopathy
and age-related macular degeneration.
There is yet no optimal therapy avail-
able for these conditions, partly due to
the fact that no good large animal
models are available for testing new
treatment options for these diseases.
Although the anatomy of the rabbit
eye is different from that in humans
and other primates, an adenovirus
(Ad) transfected rabbit model could be
useful for animal studies on the patho-
genesis of the neoangiogenesis in
angioproliferative diseases of the eye
and for the development of new
therapeutic strategies in these diseases.
In the study by Kinnunen et al.
(Kuopio, Finland), a rabbit model
using intravitreally injected AdVEGF-A
is tested. Histological analyses
revealed a dose-dependent increase in
capillary surface area and density in
the AdVEGF-A eyes, as compared with
mock-transfected eyes (AdLacZ). The
changes were maximal at 6 days after
the gene transfer and blocked by
soluble VEGF receptor-2, emphasizing
the role of VEGF-A in causing the
neoangiogenesis. Although adenovirus
transfection, due to the transient
nature of gene expression, is partly
problematic, the model presented
seems very promising as a large animal
model for testing new therapies,
including gene therapy, for angio-
proliferative eye diseases.
Bengt RippeDepartment of Nephrology,University of Lund, Lund,
Guest editor
Acta Physiol 2006, 187, 431
� 2006 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2006.1599.x 431