Light source

A study published in Nature in May and led by Ludwig Stanford’s Michelle Monje and David Gutmann of Washington University in St. Louis showed in a mouse model that neural activity triggered by light can both initiate and drive the growth of optic nerve tumors, which develop in about 15% of children diagnosed with the cancer predisposition syndrome neurofibromatosis type 1 (NF1), and can cause vision loss. Michelle’s team discovered in 2015 that neural activity fuels high grade gliomas, and that the malignant growth is driven by the shedding of a synaptic protein named neuroligin 3. She and her colleagues show in this study that the initiation of optic nerve tumors in NF-1 depends on light exposure (visual experience) of mice during a critical period 6 to 16 weeks after birth, and light deprivation in that period prevents tumor initiation. In retinal neurons, mutations that cause NF1 in the mice result in abnormal shedding of neuroligin-3, whose soluble form was found at high levels in tumors from the mouse model and patients. An experimental drug that blocks neuroligin-3 shedding also prevented development of optic nerve tumors when it was given to mice in the period when they form, and decreased tumor growth when given after tumor formation—suggesting a strategy for the prevention and treatment of this cancer.

This article appeared in the August 2021 issue of Ludwig Link. Click here to download a PDF (2MB).


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