Sightless cavefish may offer clues to eye growth, Science authors report

July 26, 2000

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Ghostly pale, sightless cavefish normally develop shrunken, degenerate orbs in place of eyes. But, very young cavefish can instead develop a normal eye after receiving the lens of a sighted, surface-dwelling fish of the same species, researchers report in the 28 July issue of the journal, Science.

This discovery may suggest a new way to study the genetic factors involved in eye growth and development, says biologist William R. Jeffery of the University of Maryland at College Park.

Such basic research ultimately may help set the stage for better understanding certain forms of sight loss, according to Jeffery, who coauthored the Science paper with Yoshiyuki Yamamoto, a postdoctoral researcher.

"Eye surgeons continue to make advances in the field of blindness research, including exciting new processes such as cornea transplantation," Jeffery says. "Our group hopes to contribute fundamental insights into the genetic factors involved in eye development and growth. Our current research focuses on identifying basic developmental mechanisms in fish embryos that can be studied in the laboratory."

Jeffery and Yamamoto can't say yet whether developing cavefish gain sight after lens transplantation. But, the small, dark-dwelling creatures suggest a simple method for quickly testing various potential eye-growth factors.

"We now have preliminary confirmation that the lens is the seat of a signaling mechanism that somehow causes the eye to grow," explains Jeffery, a professor and chairperson of biology at the university. "We think we could coat a bead with a factor of interest, such as fibroblast growth factor, which is secreted by the normal lens, put that into the cavefish eye, and watch to see if it stimulates eye growth."

As embryos, cavefish such as Astyanax mexicanus, collected in caves beneath northeastern Mexico, begin to form eyes. But, the young lens soon degenerates, so that the cornea, iris, pupil, and other optic tissues that depend on signals from the lens are absent or rudimentary, the Science paper notes. In adult cavefish, all that remains is a collapsed remnant of the eye, covered by a flap of skin.

To learn whether the lens plays a role in triggering eye growth, the research team compared the sightless cavefish with closely related, sighted fish of the same species, gathered from surface streams outside the caves. The lens precursor tissue from embryos of the surface-dwelling fish was surgically implanted into the eye cup of the developing cavefish, after its own degenerating lens tissue was removed. By implanting the lens only into one eye of each cavefish, researchers were able to compare the eye-forming capacity of the transplanted lens with the degenerating lens in the same animal.

Within eight days, Jeffery and Yamamoto began to see a larger eye on the transplanted side of the cavefish. After two months, cavefish had grown a large eye with a distinct pupil, cornea, and iris. In addition, the retina of the eye with the implanted lens showed rod photoreceptor cells, which are absent or rare in the degenerate cavefish eye. This shows that "the lens is able to stimulate the development of eye parts that have been lost during the past million or so years of cavefish evolution," Jeffery says.

When the experiment was reversed, so that surface-dwelling fish received the lens from a cavefish, the transplant failed to support eye growth. The researchers concluded, therefore, that "a change in lens signaling to other parts of the eye is a major cause of eye degeneration in cavefish." They caution, however, that other factors also may contribute to eye loss, and further investigations are underway in Jeffery's laboratory.

Someday, Yamamoto says, "Perhaps we can stop the cavefish lens from triggering eye regression, if we can learn exactly how the mechanism works."
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Research described in the Science paper was supported by the National Science Foundation. To receive a copy of the paper, call (202) 326-6440, or send e-mail to scipak@aaas.org .

American Association for the Advancement of Science

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