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Office of Neuroscience Research > WUSTL Neuroscience News > Female hormones increase risk of vision loss in rare genetic disease

Female hormones increase risk of vision loss in rare genetic disease

From the WUSTL Newsroom...

Girls with a rare genetic disorder caused by mutations in a gene known as Nf1 are much more likely to lose their vision than boys with mutations in the same gene. And now, researchers at Washington University School of Medicine in St. Louis believe they know why: Female sex hormones activate immune cells that damage the nerves necessary for vision.

The study was carried out in mice to mimic a common brain tumor arising in a genetic condition called neurofibromatosis type 1 (NF1). The findings, available online in The Journal of Experimental Medicine, suggest that blocking female sex hormones or suppressing the activation of specific immune cells in the brain could save the eyesight of children with NF1-associated brain tumors.

“The take-home message is that a child’s sex matters when it comes to this disease,” said David H. Gutmann, MD, PhD, the David O. Schnuck Family Professor of Neurology and the study’s senior author. “We’ve identified what leads to this difference in vision loss, and that suggests novel potential therapies to treat this serious medical problem in children. Understanding why boys and girls with mutations in the same gene have different outcomes presents unprecedented opportunities to fix the problem.”

NF1 causes children and adults to develop brain and nerve tumors. These tumors are typically benign – meaning they don’t spread to other parts of the body and lead to death – but they still can have serious consequences.

Nearly 20 percent of children with NF1 develop brain tumors that involve the optic pathway, affecting the nerves that carry vision-related signals from the eye to the brain. In some children, these tumors cause vision loss; however, it is not currently possible to predict who will experience vision decline and who will not.

Two years ago, Gutmann and colleagues were the first to report that girls with NF1 were five times more likely to lose their sight than boys, even though there were no clear differences in the size of the tumors between boys and girls.

To discover why girls are more likely to experience vision decline from their tumors, Gutmann, postdoctoral researcher Joseph A. Toonen and colleagues studied mice with Nf1 gene mutations specifically engineered to develop tumors on the optic pathway. Both male and female mice developed tumors that were identical in size and growth rates; however, only the female mice exhibited significant nerve damage and vision loss.

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