Featured Research

from universities, journals, and other organizations

Receptor That Enables Clear Corneas Is Identified

Date:
October 20, 2006
Source:
Medical College of Georgia
Summary:
The cornea stays clear by expressing a soluble form of a receptor that traps factors enabling growth of vision-obstructing blood vessels, researchers say.

Dr. Balamurali K. Ambati, corneal specialist at MCG and the Veterans Affairs Medical Center in Augusta.
Credit: Image courtesy of Medical College of Georgia

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 – corn1 and Pax6 mice – they found no corneal expression of sflt-1. When they gave recombinant sflt-1, the animals’ corneas cleared. Pax6 mice have a mutant version of Pax6 protein, which is involved in eye development; humans with a rare disease called aniridia, in which the irises are missing, also have this mutation.

They found the corneas of manatees, which have unusual, naturally vascularized corneas, also do not express sflt-1. Interestingly, most marine life, including whales, have clear corneas, as do shallow-water dwelling dugongs or sea cows – which are the same order of mammals as manatees – and elephants, the closest known terrestrial evolutionary relative of manatees, the researchers say.

“The correlation between sflt-1 expression and corneal avascularity in diverse mammals supports an evolutionarily conserved role for sflt-1 conferring the cloak of corneal avascularity,” they write.

The finding of sflt-1’s critical role in corneal clarity 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. Balamurali 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 in preventing angiogenesis.”

No doubt sflt-1 is vigilant, keeping blood vessels at bay when the cornea’s oxygen is compromised by contact lenses or even just sleeping. 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, such as during sleep.

As they pursue its clinical potential, researchers want to study the regulators that switch the gene from producing membrane-bound flt-1 to making the roaming soluble form. “They have the same parent gene,” says Dr. Balamurali Ambati. “Why sometimes does it make one and sometimes it makes the other? What controls the switch is of great interest.”

Other contributing institutions include Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan; Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville; Molecular and Cell Biology Laboratory, Rome; University of Florida College of Veterinary Medicine, Gainesville, Fla.; Department of Pathology, Microbiology and Immunology, University of California, Davis; Department of Pathology, Sea World, San Diego; The Eye Pathology Laboratory, Wilmer Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore; Division of Human Gene Therapy, The Gene Therapy Center, University of Alabama at Birmingham; School of Tropical Environment Studies and Geography; James Cook University, Australia; Department of Medical Genetics, University of Wisconsin, Madison; School of Medical Sciences, University of Aberdeen, United Kingdom; Department of Physiology & Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia; Institute of Medical Science, University of Tokyo, Japan; Department of Molecular Oncology, Genentech, Inc., South San Francisco; and the Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche, Naples.


Story Source:

The above story is based on materials provided by Medical College of Georgia. Note: Materials may be edited for content and length.


Cite This Page:

Medical College of Georgia. "Receptor That Enables Clear Corneas Is Identified." ScienceDaily. ScienceDaily, 20 October 2006. <www.sciencedaily.com/releases/2006/10/061018150733.htm>.
Medical College of Georgia. (2006, October 20). Receptor That Enables Clear Corneas Is Identified. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2006/10/061018150733.htm
Medical College of Georgia. "Receptor That Enables Clear Corneas Is Identified." ScienceDaily. www.sciencedaily.com/releases/2006/10/061018150733.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins