Scientists Characterize Proteome Of Human Cornea

The cornea is the transparent, dome-shaped window that covers thefront of the eye. Although it is clear and seems to lack substance, thecornea is actually a highly organized group of cells and proteins. Itsfunctions include shielding the eye from germs, dust, UV light, andother harmful matter and acting as the eye's outermost lens.

Approximately 120 million people in the United States weareyeglasses or contact lenses to correct nearsightedness,farsightedness, or astigmatism. These vision disorders are often theresult of incorrect curvature or irregular shape of the cornea and arethe most common vision disorders in this country. Other diseases thataffect the cornea range from bacterial, fungal, and viral infections(keratitis) and allergies to various dystrophies including keratoconus.

"Corneal damage and disorders account for several million casesof impaired vision and are second to cataracts as the most importantcause of blindness in the world," explains study author Dr. Jan J.Enghild of the University of Aarhus in Denmark. "Corneal infections bybacteria, fungi, or viruses are common disorders that can lead tocorneal opacification. A group of inherited corneal disorders includinggranular and lattice corneal dystrophies are characterized bydeposition of insoluble and opaque macromolecules in the cornea. Otherdisorders associated with loss of corneal transparency arise fromcornea swelling (Fuchs' dystrophy) or thinning and change of curvatureof the cornea (keratoconus)."

In order to learn more about the cornea and corneal disorders,Dr. Enghild and colleagues characterized the most abundant proteinsfound in the non-diseased human cornea. They identified 141 distinctproteins, 70% of which have not previously been identified in thecornea. This work is the most comprehensive protein study of the corneato date.

"Surprisingly, about 15% of the identified proteins in thecornea are classical blood proteins, which indicate that they originatefrom the blood stream around the cornea and are not produced in thecornea," notes Dr. Enghild. "Our results also showed that proteolysisand post-translational modifications of proteins are common events inthe normal human cornea."

Among the molecules that the scientists identified wereproteins involved in antimicrobial defense, heme and iron transport,tissue protection against UV-radiation and oxidative stress. Severalother proteins were known antiangiogenic factors, which prevent theformation of blood vessels.

The results from this research may open the door to futuretherapeutics for a myriad of corneal disorders. "It is essential toknow the biochemical composition of normal healthy corneas in theeffort to understand the molecular mechanisms behind cornealdisorders," emphasizes Dr. Enghild. "By comparative proteomic studiesof diseased and normal corneas we can identify differences in theexpression profiles that may suggest avenues for therapeuticinterventions. Because the cornea is so accessible, the potential fordeveloping effective drugs for the treatment of corneal diseases isgood. Furthermore, the work is likely to improve the clinicalclassifications of corneal diseases. Identification of the proteinprofile of the normal human cornea may also be very useful in theeffort toward generating artificial corneas for transplantation."

To follow up on their initial research, Dr. Enghild and hiscolleagues have begun proteomic studies of corneas affected by granularand lattice corneal dystrophies, and are also planning on looking atother cornea diseases such as keratoconus and Fuchs' dystrophy.

The American Society for Biochemistry and Molecular Biology (ASBMB)is a nonprofit scientific and educational organization with over 11,000members in the United States and internationally. Most members teachand conduct research at colleges and universities. Others conductresearch in various government laboratories, nonprofit researchinstitutions, and industry.

Founded in 1906, the Society is based in Bethesda, Maryland, onthe campus of the Federation of American Societies for ExperimentalBiology. The Society's primary purpose is to advance the sciences ofbiochemistry and molecular biology through its publications, theJournal of Biological Chemistry, the Journal of Lipid Research,Molecular and Cellular Proteomics, and Biochemistry and MolecularBiology Education, and the holding of scientific meetings.

For more information about ASBMB, see the Society's website at www.asbmb.org.

The manuscript for the Molecular and Cellular Proteomics paper can be downloaded from the following URL:http://www.mcponline.org/cgi/content/abstract/D500003-MCP200v1