Comprehensive Ophthalmology, Retina/Vitreous

Scientists from the National Eye Institute have discovered that the breast cancer drug tamoxifen may have a protective effect on photoreceptors, offering a potential new way to treat retinal diseases.

Although typically used for cancer treatment, the selective estrogen receptor modulator tamoxifen is also used as a tool in the laboratory to activate specific genes in genetically engineered mice.

That’s how Wai Wong, MD, PhD, chief of NEI's Unit on Neuron-Glia Interactions in Retinal Disease, was using tamoxifen in his lab when he and his team noticed something surprising – mice treated with tamoxifen gained resistance to light-induced eye injuries.

In his paper published in the Journal of Neuroscience, Dr. Wong exposed mice to short-duration, high-intensity light to induce photoreceptor degeneration. But the tamoxifen-treated mice were protected from photoreceptor apoptosis and atrophy, while maintaining near-normal levels of electroretinographic responses.

This finding was confirmed in a genetic (Pde6brd10) model of retinitis pigmentosa, showing tamoxifen significantly improved retinal structure, electrophysiological responses, and visual behavior.

Wong believes that tamoxifen’s protective effect is mediated through microglia in the retina that remove and kill photoreceptor cells in response to light injury.

“The immune system becomes alerted to the stressed photoreceptors and goes into culling mode, clearing them out of the retina,” Wong explained.

While the mechanism of action is unknown, in vitro studies suggest that tamoxifen inhibits this microglia-mediated immune response, rather than directly protecting the photoreceptors. Wong and his team are now studying how tamoxifen inhibits microglia at a molecular level.

Wong used high-dose tamoxifen in his study, equivalent to 8 times the FDA-approved dose for breast cancer. Investigations into the efficacy of lower doses are underway, and will likely set the foundation for future clinical trials, which Dr. Wong and his team expect to take place soon.

“Translation to the clinic can happen reasonably rapidly because tamoxifen, as an FDA-approved drug, already has a well-characterized safety profile,” he explained.