Study of Cavefish DNA Holds Insight for Human Blindness

WASHINGTON (CN) – Touting a new study of cave-dwelling fish that evolved to be eyeless, a research team reported Tuesday that its findings could lead to treatments for people who are blind.

While a surface variety of the fish Astyanax mexicanus has eyes (top) the cave morph (bottom) loses its eyes soon after development. (Photo by Daniel Castranova, NICHD/NIH)

Known as A. mexicanus, the tropical fish that inspired the paper published Sunday in the journal Nature Ecology & Evolution is distinctive because no obvious genetic mutation caused the cave-dwelling variety, or morph, of the fish to lose its eyes.

Indeed the cave morphs and a surface variety of A. mexicanus whose eyes are intact have similar genomes and can interbreed.

Cave morphs do begin developing eyes early in their lives but their eyes degenerate within a few days. Researchers theorize that the eyeless cavefish variety arose a few million years ago when some A. mexicanus fish got trapped in dark caves.

What Sunday’s research paper announces is that, rather than a genetic mutation that effects permanent changes in the DNA code, an epigenetic process called DNA methylation actively silences the eye-development genes of these blind cavefish.

“Epigenetic regulation is a process where genes are turned off or on, typically in a reversible or temporary manner,” according to a press release on the study from the National Institutes of Health, whose National Eye Institute provided some funding.

Sunday’s study brought together researchers from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the University of Maryland, College Park.

Brant Weinstein of the NICHD noted in an interview Tuesday that human eyes express 26 of the same genes that limit eye development in the cavefish. Of these 19 are linked to human eye disorders.

“Although additional work needs to be done to better understand how DNA methylation influences the expression of these genes, these findings could help in developing therapies that can compensate or alleviate defects in these genes,” Weinstein said in an email.

Weinstein noted that research on blood disorders has also lent support for the theory that epigenetic processes play a key role in different blood cancers or leukemias.

“In the future,” Weinstein said, “it will be interesting to determine how many eye disorders are similarly caused by changes in the epigenetic regulation of key eye genes.”

Through the epigenetic process, the DNA of developing eyes in cavefish is tagged with a protein called DNA methyltransferase. When researchers mutated the same protein in zebrafish, the mutant zebrafish exhibited larger eyes and more active eye genes.

Sunday’s paper says such results suggest that something happened in the evolution of cavefish to elevate the protein also known as DNMT3B, leading to epigenetic suppression of eye development genes.

“Our study indicates that small genetic changes that alter epigenetic regulation can play an important role in evolution by triggering dramatic changes in the expression of large sets of genes,” Aniket Gore, who is the study’s lead author, said in a statement.

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