a new large animal model for studying and testing treatments of angioproliferative eye diseases

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,

Finlandpasi.tavi@oulu.fi

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,

Swedenbengt.rippe@med.lu.se

Guest editor

Acta Physiol 2006, 187, 431

� 2006 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2006.1599.x 431