The transparent cornea, located in the front of the eye, acts not only as a refracting medium to focus light on the retina and help us see, but also serves as the main barrier and structure in the front of the eye. Serious disease of the cornea can lead to blindness accompanied by severe pain. Corneal diseases and injuries are the leading reason for visits to eye care clinics in the U.S. today. Two important areas for research on the cornea are: 1) to explore and understand the molecular basis of corneal transparency, and 2) to analyse the molecular nature of corneal wound healing and inflammation. ? ? We previously developed a new clinical device to understand molecular changes that occur in the lens, the NASA-NEI Dynamic Light Scattering (DLS) device. Laboratory studies have shown its potential in the detection of the earliest molecular changes occuring in cataracts. Clinical studies on the lens have also shown good reproducibility, sensitivity to pick up small changes, and safety of the non-invasive, in vivo DLS clinical cataract system. ? ? We initially conducted laboratory studies in animals to determine if the DLS laboratory probe/device is also useful to study the cornea. We found that the DLS lab probe can detect molecular differences in various layers/compartments of the cornea in the normal state. In addition, we found that after corneal injury such as after laser photorefractive surgery, chemical injury and scraping, the DLS could detect changes which are not apparent or detectable using optical devices such as the slit lamp biomicroscope. This suggest that the DLS may be useful as a non-invasive, in vivo device to study the cornea in the normal state as well as in diseased states and to understand the molecular basis of corneal transparency.? ? In this pilot project, in collaboration with Drs. Rafat Ansari and Kwang Suh, physicists from NASA-John Glenn RC in Cleveland, Ohio, and undet the NASA-NEI Inter Agency Agreement, a new NASA-NEI DLS clinical device was created for the cornea, based on the same platform as the cataract device (on the Keratron Corneal Mapping System from Italy which has the 3 dimensional aiming system, and the NASA space shuttle DLS probe). After a number of stages of DLS device modifications done by our NASA collaborators (engineers and physicists) based on trial and error tests on our volunteers, we have now obtained good repeatable corneal measurements. We therefore examined 30 volunteers and recruited patients with normal as well as abnormal corneas after careful slit lamp examination and testing. All patients gave full informed consent and underwent comprehensive eye examinations, as required by the NEI-IRB approved Protocol. They then underwent DLS testing, which took 10-15 minutes after the eye examinations.? ? We found the following intersting findings: First, the DLS clinical device detected basic differences in protein composition between cornea, lens and vitreous, and showed distinct signals from corneal glycoproteins and collagen. Second, in comparing normal and diseased corneas, there were distinct differences in protein composition between normal, diabetic and post surgical (LASIK) corneas. In normal corneas, there are 2 protein groups, one in the 1000 nm diameter size and another in the 5000 nm size. In post LASIK corneas, there is a peak in the 1000 nm size but the second peak (larger molecular weight) is in the 8000 nm size area. In diabetics, the lower molecular weight group ranges from about 200 to 1000 nm size (wider spread) and the large molecular weight proteins are spread from 2000 to 25,000 nm size (much wider spread). ? ? These were all performed easily and safely, in vivo (clinically), objectively and non invasively. These findings suggest that this new DLS clinical corneal device may be useful in detecting and studying corneal abnormalities in the molecular level. In particular, it may be useful in detecting corneal problems after LASIK surgery as well as in diabetes and other disorders. It will also be useful in solving other problems, such as in differentiating between LASIK treated and non LASIK treated corneas among eye bank eyes donated for transplant patients, which at this time are very difficult to distinguish from each other by clinical means, posing a danger to transplanted patients.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000407-04
Application #
7322411
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cortes, Lizette M; Mattapallil, Mary J; Silver, Phyllis B et al. (2008) Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Invest Ophthalmol Vis Sci 49:1946-56