Corneal transparency depends on corneal endothelial cells

August 15, 2005

Fort Lauderdale, FL—The structures in the cornea maintain a fine balance that keeps the corneal tissue transparent said Henry F. Edelhauser, PhD. He described those structures and the events that lead to break-down of the corneal endothelial cells and corneal edema at the annual meeting of the Association for Research in Vision and Ophthalmology.

Fort Lauderdale, FL-The structures in the cornea maintain a fine balance that keeps the corneal tissue transparent said Henry F. Edelhauser, PhD. He described those structures and the events that lead to break-down of the corneal endothelial cells and corneal edema at the annual meeting of the Association for Research in Vision and Ophthalmology.

"Corneal transparency is an interesting phenomenon. The corneal endothelium is a very important tissue in maintaining corneal transparency by maintaining its barrier and the metabolic pump," said Dr. Edelhauser, who delivered the Proctor Lecture, the association's most prestigious award. "Loss of either of the metabolic pump or the barrier function results in corneal edema and loss of transparency."

He used the sea lamprey to demonstrate corneal structure and the differences in the structure among species. This fish has an anterior spectacle and the cornea develops under the skin of the spectacle; the spectacle is a non-swelling tissue because of the presence of sutural fibers. The marine teleost fish has an anterior and posterior stroma that are separated by a mucoid tissue containing pigmented granules. Sharks have a thin cornea that is also non-swelling with loosely attached endothelial cells. Trout have a thick epithelium and a primitive corneal endothelium.

In the rabbit endothelium during development, there is a progressive decrease in endothelial cell density, resulting in decreased permeability of the endothelium, the establishment of the metabolic pump, and a decreased tissue hydration.

In humans, the number of endothelial cells also decreases rapidly with development during the first 5 years of life to reach about 2,500 to 3,000 cells/mm2 in adulthood. In addition, the peripheral cornea has increased endothelial cell density compared with the center of the cornea. Some factors to consider in light of the increased peripheral cell density are the regenerative potential of endothelial cells and the presence of a peripheral storage region of cells, explained Dr. Edelhauser, director of research, department of ophthalmology, Emory University Eye Center, Atlanta.

When he and his colleagues compared the endothelial cell densities at the limbal, paracentral, and central areas in eye bank corneas in specimens from 19-, 33-, and 75-year-old individuals, they found that in all cases there is an increase in peripheral endothelial cell density compared with the central endothelial cell density.

"That population of endothelial cells in the peripheral cornea is maintained throughout life," he said.

Another interesting finding is that the corneas in older Japanese individuals have many more endothelial cells compared with an older Caucasian population. An 80-year-old person from Osaka, Japan, Dr. Edelhauser noted, has as many endothelial cells as a 20-year-old Caucasian from Milwaukee, WI.

To determine the potential of the endothelial cells, Dr. Edelhauser and associates recently examined the mouse, the rabbit, the rat, the rhesus monkey, the baboon, and the macaque and found that the animals do not have increased peripheral cell density as human do. For example, the macaque has uniform endothelial cell density in the central and peripheral cornea from ages 6 to 16 years.

"The human endothelium, therefore, is somewhat unusual," he said. "With the increased number of endothelial cells in the periphery of the human cornea, the question then arises about whether there are peripheral endothelial stem cells."

To find out if endothelial cells divide, Dr. Edelhauser examined 25 pairs of human corneas from individuals aged 22 to 75 years and found that only seven corneas stained with 5-bromo-2'-deoxyuridine (BrdU) indicated that there was a possibility of cellular mitosis. Another experiment in which a fluorescent-labeled BrdU was used showed the endothelial cells were stained more in the cells adjacent to Schwalbe's line.

In a study in which he and his colleague isolated central endothelial cells and compared them with endothelial cells from the periphery, they found telomerase activity in the peripheral cells, which is usually found in fetal cells, germ-line cells, cancer cells, and stem cells.

There is, however, no definitive answer about the presence of stem cells in the human cornea. Dr. Edelhauser said this is a fertile research area that should be pursued because it is possible that the peripheral corneal endothelium has stem cells.