Genetics of blind cave fish lays ground for treating eye disease

University researchers led a collaborative effort between 10 universities.

Haley Madderom

An international team of researchers hopes to use its study on a species of translucent, eyeless cave fish to better understand human conditions like degenerative eye diseases, albinism and sleep disorders.

The first-ever genomic sequence of the blind cave fish species, and the resulting study published late last month, provides context for a field of research where knowing species’ exact genetic makeup is valuable.

Researchers say the most distinctive trait highlighted in the study — which is the complex genetics of eye degeneration — could have major implications for humans, like helping with the development of gene therapies for patients with retinitis or macular degeneration.

Geneticists have long been fascinated by Astyanax mexicanus because populations of the blind cave fish species vary greatly between water surface and cave populations — the latter of which has independently evolved traits of blindness and lack of pigment, said Suzanne McGaugh, the study’s lead researcher and an ecology, evolution, and behavior associate professor.

“It’s really powerful to have a very closely related relative that you can compare sequenced DNA to and say what’s different between these two [types of populations],” she said.

McGaugh said the work was not aimed at developing potential therapies for particular human ailments. Instead, researchers located specific genes that affect traits related to various diseases to bolster continuing medical and evolutionary research.

In particular, they focused on the genetics behind retinitis pigmentosa, an inherited retinal disease that leads to tunnel vision and night blindness, as well as total blindness in severe cases.

To counteract the human disease, specialized gene therapies would have to address the more than 80 different genes associated with the illness, some of which have not been located yet, said ophthalmology assistant professor Sandra Montezuma.

Ophthalmology assistant professor Dara Koozekanani, who was not a part of the international effort, said the cave fish study could play a pivotal role in eye disease research.

“Any addition to our knowledge of these degenerations can hopefully help us to develop effective treatments,” he said.

McGaugh said the genomic sequencing work could apply to more than just patients with eye diseases and help with identifying genes related to changes in sleep patterns, pigment loss, feeding behaviors and aggression. The October study also gives geneticists insight into the evolutionary process, she said.

The study was a joint effort from 10 institutions both in the U.S. and in Europe, each of which contributed results of their own work.

“It’s by far not just my lab,” McGaugh said. “In fact, this is a really new part of research for me.”

Bethany Stahl, a doctoral biology student at the University of Cincinnati, was part of the effort. She said she is using the results of the cave fish study for her dissertation on pigment loss.

“I’m getting close to uncovering some additional genes that are involved in pigmentation variation,” Stahl said.

Her lab’s contribution to the research involved using RNA sequencing to map out the rate of gene expression in fish during early stages of development.

The lab also performed a common “knock out” test that turned off particular genes in an organism to understand the effects of the genes’ absences. The test could help understand pigmentation, sleep and behavioral changes, and jaw bone formation.

“I feel very fortunate to be involved in such a very forthcoming and exciting project,” Stahl said.