It’s a question that has long perplexed scientists: Why do girls who develop a rare type of benign brain tumors lose their vision more often than boys?
Finally, an answer: A female hormone causes tumors that arise from a genetic condition called neurofibromatosis type 1 (NF1) to release a toxin that damages optic cells.
The findings by researchers at Washington School of Medicine in St. Louis were published Tuesday in The Journal of Experimental Medicine.
“The take-home message is that a child’s sex matters when it comes to this disease,” said Dr. David H. Gutmann, the study’s lead author, in a Washington University news release. “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.”
Gutmann and his colleagues arrived at their conclusions after conducting experiments on mice with NF1 gene mutations “specifically engineered to develop tumors on the optic pathway,” according to the news release. “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.”
The researchers discovered that the tumors of the female mice contained more of an immune cell known as microglia. Further experiments showed that female hormones caused the immune system to produce the microglia.
The discovery was made by removing the ovaries from the female mice and the testes from the male mice. While no differences were found in the amount of microglia in the male mice upon castration, the female mice post-hysterectomy contained less microglia and “fewer cells in the retina died,” the news release reported. “Moreover, the researchers identified the specific nerve-damaging toxins produced by these activated microglia.”
With a cause for the vision loss in hand, researchers can now target the damaging compounds in creating new medicines to combat the problem.
“This sex difference has turned out to be critical for us to begin to unravel the causes of the vision loss in NF1-optic tumors,” Gutmann said in the news release. “We would not have identified the key molecular signals that promote neuronal death without these sex differences. Moreover, these findings have implications beyond brain tumors that have led us to explore sex differences in other NF1 neurological problems, including autism, sleep and attention deficit.”
According to the National Institutes of Health, NF1 affects 1 out of every 3,000 to 4,000 people in the U.S.
“Children with NF1 may have poor language and visual-spatial skills, and perform less well on academic achievement tests, including those that measure reading, spelling and math skills,” the NIH reports. “Learning disabilities, such as attention deficit hyperactivity disorder (ADHD) , are common in children with NF1.”
A professional journalist nearly 30 years, David Heitz started his career at the Quad-City Times in Davenport, Iowa before moving to Los Angeles. He led the Glendale News-Press to best small daily newspaper in the state (CNPA) as managing editor and also worked as executive news editor of the Press-Telegram. He worked briefly as deputy news editor of the Detroit News before returning to the Quad-Cities, where he has worked as a freelance medical writer since 2012 for several national websites. He recently purchased his childhood home and says he truly is “living the dream.”
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