How a molecule in the cornea could help fight blindness—and maybe cancer
by Patrick Kenney
This is how scientific discovery begins; a question that doesn’t have an answer meets intelligent people who won’t rest until they find one.
“Why is it that the cornea is clear?”
Dr. Dimitri Azar, interim dean, College of Medicine professor and head of the department of ophthalmology and visual sciences at the University of Illinois College of Medicine says this particular inquiry led to an exciting discovery and opened a new frontier in medicine.
The cornea is the clear, outer layer of the eye and the first step toward healthy vision. The cornea allows light to pass through it and helps to focus the light through the lens onto the back of the eye, the retina, where it is processed, and an image is sent to the brain through the optic nerve. In order for this to happen, it’s essential that the cornea remain clear.
When you sustain an injury, for example when you trip and scrape your palm on the sidewalk, your body immediately begins a multilayered healing response. Part of this response is the growth of new blood vessels. The scrape on your hand requires an extra supply of blood to fight infection and begin rebuilding the skin.
When the cornea sustains an injury, the body rushes to heal it. But because the cornea must remain clear in order to preserve healthy vision, the body skips the step involving the growth of new blood vessels, which would cloud the cornea and obstruct vision.
“It is a very intriguing observation that corneal wound healing is different from healing in other parts of the body,” says Azar. But for scientists like Azar, observing the phenomena is not enough. It must be understood.
“The reason that the cornea remains clear after most injuries is because of the production of very potent antiangiogenic molecules in the cornea,” says Azar. These molecules prevent blood vessel growth. “And [they] allow the remainder of the cascade of wound healing to occur without needing blood vessels.”
Angiogenesis is the fancy word for blood vessel formation. As mentioned, the body’s angiogenic response to injury is usually a good thing. But in the case of the eye, new blood vessel formation is usually a sign of trouble.
The retina, the membrane at the back of the eye, does not posses the antiangiogenic ability of the cornea. When new blood vessels begin forming here, there are no special molecules to stop them. Unnecessary new blood vessels forming at the back of the eye are part of a condition called wet age-related macular degeneration, one of the leading causes of blindness in seniors.
“We think of it as a healing response that went awry,” says Dr. Mathew MacCumber, associate professor and associate chairman for research, department of ophthalmology at Rush University Medical Center.
“The layer of cells that is typically affected in age-related macular degeneration (AMD) is called the retinal pigment epithelium (RPE). These are the cells that sit right under the photoreceptors—the special neurons that detect light,” explains MacCumber. “The photoreceptors have a portion of their photosensitive cell membranes removed and replaced each day by the RPE. But over time, after decades of using our eyes, the system in some individuals stops being as efficient, and there’s buildup of [waste] material. The first visible sign of AMD is yellowish deposits under the RPE called drusen, which are believed to be these waste materials.”
If that’s hard to follow, think of it this way; the rods and cones of your retina are like your color printer, and your hands do the work of the retinal pigment epithelium. As ink cartridges are used up by your printer you replace them with new ones and dispose of the old ones. But if you lost the ability to dispose of the cartridges properly and began pulling them out of the printer and dropping them next to it, soon you’d have a real mess.
It’s this mess that the body is trying to fix when it calls out for the formation of new blood vessels. “It’s the body’s attempt to improve the situation, but it actually makes things worse,” says MacCumber.
What if you could harness the antiangiogenic powers of the cornea and give them to the retina?
“You can see the potential for the future,” says Azar. “Not only will we be able to allow for better healing in the cornea, which was our original goal, but by identifying these naturally occurring molecules that inhibit blood vessel growth, there is great potential to apply them in situations where blood vessel growth causes serious problems, such as macular degeneration or even cancer.”
But wait, we’re talking about the eye. How can these antiangiogenic molecules found in the cornea be used to fight cancer elsewhere in the body?
One way of treating cancer is by shrinking the blood vessel network that feeds the cancer cells,” explains Azar. “Borrowing some of the mechanisms of wound healing, cancer cells produce molecules that allow surrounding tissues to produce blood vessels that allow for greater growth of tumor cells.”
As the body attempts to solve the problem of the cancer, again using its normal methods involving blood vessel formation, it is in fact feeding the cancer. “Cancer will grow at a faster rate as it develops stronger networks of blood vessels that feed the cancer cells,” says Azar.
“There is an opportunity to translate that research from the laboratory bench to the patient’s bedside; there may be a role for the corneal-derived antiangiogenic molecules in inhibiting the growth of cancer cells,” says Azar.
That takes time and resources. These antiangiogenic molecules discovered in the cornea aren’t likely to cure macular degeneration or cancer, but they could lead to powerful new drugs in the fight against both.
Perhaps most importantly, where there was a question, there is now an answer. And as has happened countless times before in science and medicine, the answer brings with it a whole new series of questions.[email_link]
Published in Chicago Health Winter 2012