JCI online early table of contents: May 15, 2008

EDITOR'S PICK: Look to the future: new drug reduces one cause of vision loss

In the industrialized world, most diseases that cause vision loss do so by altering the permeability of the blood vessels in the retina of the eye such that fluid accumulates in the retina impairing eyesight. For many of these diseases, the molecule VEGF is the initiator of increased blood vessel permeability and recent clinical data have indicated that VEGF antagonists can stabilize, or even improve, the eyesight of some patients. However, such treatment requires repeated injection of the VEGF antagonist into the eye. A potentially more painless and simple approach to reducing VEGF-induced blood vessel permeability in the eye has now been suggested by the work of Martin Friedlander and colleagues, at The Scripps Institute, La Jolla, in mouse and rabbit models of increased VEGF-mediated blood vessel permeability.

In the study, a small molecule inhibitor of the signaling molecules that associate with the receptors of VEGF (which are known as Src kinases) was found to eliminate VEGF-induced accumulation of fluid in the retina of mice and rabbits. This effect was observed both when the inhibitor was injected intravenously and when the inhibitor was administered in an eye drop. The specificity of the approach was confirmed by showing that the inhibitor did not prevent VEGF-induced accumulation of fluid in the retina of mice lacking the Src kinases that associate with the receptor of VEGF. The authors therefore suggest that future studies should investigate whether this approach would be of benefit to individuals with the many diseases that cause vision loss through VEGF-induced increased blood vessel permeability.

TITLE: Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits

AUTHOR CONTACT:
Martin Friedlander
The Scripps Research Institute, La Jolla, California, USA.
Phone: (858) 784-9138; Fax: (858) 783-9135; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33361

CARDIOLOGY: Genetic mutation causes seizures and an irregular heartbeat

Exercise or becoming highly emotional can cause the heartbeat to become irregular, often causing sudden death, in individuals with an inherited heart disorder known as catecholaminergic polymorphic ventricular tachycardia (CPVT). The gene that is mutated in many individuals with CPVT carries the information for making a protein known as RyR2, which forms a channel through which Ca2+ passes. The genetic mutations in individuals with CPVT make the RyR2 channel leaky and this is thought to cause the potentially fatal irregular heartbeats. A large proportion of individuals with CPVT also suffer from seizures and these were thought to be caused by changes in the heartbeat. However, Andrew Marks and colleagues, at Columbia University College of Physicians and Surgeons, New York, have now generated data in mice indicating that the seizures are directly caused by leaky RyR2 channels.