Scientists may have found a new way to block a chain of molecular signals leading to the most common form of blindness. A compound that blocks the receptor for a signaling molecule successfully prevented half the growth of blood vessels rampant in the eyes of newborn mice. The condition can blind infants born prematurely, persons with diabetes, and the elderly, a team reports in this month Nature Medicine .
When the eyes are low in oxygen, the cells that line the retina send chemical distress signals. Such alarm, a molecule called vascular endothelial growth factor (VEGF), is trying to save the day by sprouting of new blood vessels. Ultimately, however, it spoils the rescue by causing the formation of leaking vessels - a condition known as hypoxia-induced proliferative retinopathy. Probing this chain of events, ophthalmologist Lois Smith and colleagues at Harvard Medical School and Hospital Boston Children examined the role of a signaling molecule called insulin growth factor-1 (IGF-1), which had been linked to the VEGF action in mice and humans.
Smith began imitating retinopathy in neonatal mice. She placed 7 days of age the pups and their nursing mothers in rooms infused with 70% oxygen and then removed animals after 5 days. As for premature babies, the lower oxygen concentration, oxygen-free in the eyes of infants. The researchers then gave newborns daily injections of either a peptide known to block the receptor for IGF-1 or control. Five days later, the growth of blood vessels in mouse eyes that received the inhibitor is half that of control animals.
The mechanism is not straightforward. Rather than blocking the production of VEGF, the compound prevents the receptor for IGF-1 release of the VEGF receptor, which normally remains on the order to make new blood vessels. The reason that some blood vessels have continued to grow in laboratory animals, Smith suggests, is that the signaling compounds other than IGF-1 may still be in operation.
"This study is interesting and shows that there is some interaction between IGF-1 and VEGF signaling pathways," said Peter Campochiaro ophthalmologist at Johns Hopkins Medical School in Baltimore, a researcher retinopathy long. But he believes that IGF-1 may not be the best receiver to target. Campochiaro and colleagues plan to start clinical trials on a VEGF receptor antagonist that is 100% effective at blocking VEGF. It is not yet known if this more radical approach will be safe in people. "What we're trying to do is look at the more complex interactions so that we can better modulate these pathways for clinical use," says Smith.
0 Komentar