Receptor That Enables Clear Corneas Is Identified
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, teams of researchers led by the Medical College of Georgia and University of Kentucky report in Nature. The paper was published online Oct. 18 and will be in the Oct. 26 print issue.
"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 role in corneal clarity opens the door for exploring its use to eliminate unwanted blood vessels in the cornea that can follow injury, including contact lens use or a chemical burn, as well as blinding proliferation occurring in the retina with 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 of the cornea, which lets light into the eye and focuses two-thirds of it.
"The molecule responsible for corneal avascularity is much like the holy grail of vascular biology and our identification of VEGF receptor-1 as that candidate has far-reaching implications for a variety of neovascular diseases such as macular degeneration, diabetic retinopathy, cancer and atherosclerosis," said Dr. Jayakrishna Ambati, ophthalmologist and vice chair of the University of Kentucky Department of Ophthalmology & Visual Sciences.
In two animal models known to have blood vessels in their corneas