Target Health Blog

NIH Research Shows How Eye Loss Occurs in Blind Cavefish

July 2, 2018

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Ophthalmology
Source:

The “blind cavefish“ Astyanax mexicanus, is a tropical freshwater fish native to Mexico. A few million years ago, some of these fish presumably got trapped in dark caves and gave rise to completely different varieties, or “morphs,“ that lack eyes and have several other unique physical, behavioral and physiological changes. Despite their dramatic differences, surface and cave morphs share similar genomes and can interbreed. Cave morphs begin eye development early but fail to maintain this program, undergoing eye degeneration within a few days of development. Previous research has not revealed any obvious mutations in genes important for their eye development.

According to a study published online in Nature Ecology & Evolution (28 May 2018) an NIH sponsored research study showed how eye loss occurs in the blind cavefish. Results showed that loss of eye tissue in the blind cavefish, which occurs within a few days of their development, happens through epigenetic silencing of eye-related genes. Epigenetic regulation is a process where genes are turned off or on, typically in a reversible or temporary manner. This mechanism differs from genetic mutations, which are permanent changes in the DNA code. The study team found more DNA methylation of eye development genes and subsequently, less activity of these genes in the cavefish. DNA methylation is an epigenetic process in which DNA is modified with tags called methyl groups. These tags, which are added by proteins called DNA methyltransferases, silence genes by making the DNA inaccessible.

According to the authors, many of the cavefish genes identified in the study are also linked to human eye disorders, suggesting these genes are conserved across evolution and may be similarly regulated in people. The study showed that the epigenetic-based silencing of a large set of genes limits the eye development of the cavefish and that 26 of these genes are also expressed in human eyes, and 19 are linked to human eye disorders. The authors found that cavefish have higher levels of a DNA methyltransferase, called DNMT3B, in their developing eyes. When the study team mutated DNMT3B in another type of fish with eyes, zebrafish, they discovered that the mutant zebrafish have more active eye genes and larger eyes. The results suggest that a genetic change resulting in elevated DNMT3B levels occurred during the evolution of cavefish, leading to epigenetic suppression of eye development genes.

According to the authors, the results from this study may yield potential clues to understanding eye disease and blindness in people.

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