Receptor that enables clear corneas is identified
by Toni Baker
The cornea stays clear by expressing a soluble form of a receptor that traps factors enabling growth of vision-obstructing blood vessels, researchers say.
When sflt-1, a free-floating receptor for vascular endothelial growth factor A, is eliminated, vision-obstructing blood vessels start growing, reported teams of researchers led by MCG and the University of Kentucky in the Oct. 26 issue of Nature.
“Sflt-1 is a handcuff, essentially,” says Dr. Balamurali K. Ambati, corneal specialist at MCG and the Veterans Affairs Medical Center in Augusta and the study’s first author. Using multiple approaches to unlock those cuffs, from neutralizing antibodies to gene ablation, mice corneas consistently developed blood vessels.
“The standard paradigm has been the cornea is avascular because it has lots of anti-angiogenic molecules. And it does,” he says. “But knockdown of the others does not cause blood vessels to enter the cornea.”
Flt-1’s role as VEGF receptor has been known; it is abundant on cell membranes of blood vessel walls where it helps initiate blood vessel growth. In fact, its soluble form has been studied for anti-tumor potential.
However, its newfound critical role in corneal clarity suggests its use in eliminating unwanted blood vessels in the cornea caused by injury, macular degeneration and diabetic retinopathy.
“If we understand what keeps the cornea avascular in the first place, that will hopefully help us restore it when that is breached,” Dr. Ambati says.
The finding also opens a Pandora’s box because the avascular tissue is typically used to study drugs that stop dangerous new blood vessel growth that can occur with cancer, diabetes and macular degeneration.
“The cornea is a logical place to study these drugs because you don’t have to wonder which blood vessels are abnormal: they all are,” says Dr. Ambati. “But the finding that sflt-1 is responsible for corneal avascularity has implications for the relevance of these tests because we would want to know if a candidate drug is really working or working through sflt-1 is preventing angiogenesis.”
No doubt sflt-1 is vigilant, keeping blood vessels at bay when the cornea’s oxygen is compromised by contact lenses or sleep. Since the cornea is avascular, it counts on air for oxygen, so any barrier, even an eyelid, could cause problems. Instead, researchers found levels of the VEGF-binder increase dramatically when oxygen availability drops.
As they pursue its clinical potential, researchers want to study the regulators that switch the gene from producing membrane-bound flt-1 to the roaming soluble form. “They have the same parent gene,” says Dr. Ambati. “Why sometimes does it make one and sometimes the other? What controls the switch is of great interest.”