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 leads to opacification and blindness. Corneal diseases and injuries are the leading reason for visits to eye care clinics in the U.S. today. These diseases are also some of the most painful eye disorders. 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 developed a new clinical device to understand molecular changes that occur in the lens, the NASA-NEI Dynamic Light Scattering (DLS) device, which could also be useful in the Cornea. Laboratory studies have shown its potential in the detection of the earliest changes occuring in cataracts. Clinical studies on the lens have also shown good test-retest 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 device is also useful to study the cornea. We found that it 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, we studied normal, post surgical and diseased corneas in volunteers. In preliminary testing, it was determined that the DLS clinical cataract device is not properly suited for the cornea. This is because of the difference in thickness between the cornea and the lens (0.5 mm in the human cornea versus 3-4 mmm in the human lens), so that the angle of entry of the Helium Neon Light beam versus the angle of the APD light detector is not correct. Hence we developed a new NASA-NEI DLS device for the cornea. After a number of stages of DLS device modifications done by our NASA collaborators (engineers and physicists) based on tests on our volunteers, we have now obtained good repeatable corneal measurements. We found the following: First, the DLS 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 changes after LASIK surgery as well as in diabetes and other disorders.
| 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 |
