Lens, RPE may act jointly to influence differentiation

The mechanisms by which the lens influences retinal growth and differentiation during vertebrate eye development are unclear, but recent studies in surface-dwelling fish and blind, cave-dwelling fish suggest that the lens acts in concert with another optic component, most likely the retinal pigment epithelium (RPE), to promote retinal survival, said William Jeffery, PhD, a professor in the Department of Biology, University of Maryland, College Park.

Dr. Jeffery has studied eye development in two forms of the species Astyanax mexicanus, a Mexican tetra. He found that the cavefish eye is similar to that of the surface fish during the first 20 hours of embryonic development, but after that point the eye of the surface fish continues to grow, while the lens of the cavefish degenerates and dies through apoptosis. The retina also begins to show signs of apoptosis shortly after.

Studying cell proliferation, Dr. Jeffery had to resolve an enigma: the eye of the cavefish stops growing, but new cells continue to form.

"The conclusion of these studies is that cavefish retina differs from surface fish retina in that new cells are born in the ciliary margin zone and other places and begin to migrate into the retina but do not differentiate and die," he said. "There are cycles of cell division an cell death that occur in the cavefish retina that balance the situation so that there is no net growth."

He has also experimented with reciprocal eye transplantation in fish hybridized to have small eyes and wild-type surface fish. This experiment showed that the lens controlled the size of the entire eye; a small lens transplanted into a wild-type fish resulted in a smaller eye characteristic of the hybrid, and a normal eye transplanted into the hybrid produced a larger eye. Through additional experiments, he discovered that lens deletion alone does not induce retinal apoptosis and concluded that another tissue works with the lens in controlling growth.

Dr. Jeffery believe this tissue is RPE because it shows apoptosis in cavefish, is missing and does not become pigmented, and in surface fish, RPE grows around the eye cup of a deleted lens and could replace it molecularly and geographically.