Boosting the potency of a broccoli-related compound yields a possible treatment for age-related macular degeneration
Buck researchers boosted the potency of a broccoli-related compound by ten times and identified it as a possible treatment for age-related macular degeneration (AMD), the leading cause of vision loss affecting more than 10 million older Americans.
The research, published in Scientific Reports, also highlights the role of lipid metabolism in maintaining the health of the retina, reporting that palmitoleic acid also had protective effects on retinal cells in culture and in mice.
The “good-for-you” compound in broccoli which prompted the inquiry is indole-3-carbinol (I3C), which is currently being studied for cancer prevention. I3C helps clear cells of environmental toxins by activating the aryl hydrocarbon receptor (AhR) protein which upregulates pathways involved in chemical detoxification. AhR, which declines with age, is important for detoxifying the retina. Previous studies show that AhR-deficient mice develop a condition which looks extremely similar to AMD. When contemplating the possibility of boosting AhR via broccoli’s I3C, Buck faculty and lead author Arvind Ramanathan, PhD, knew there was a challenge – I3C is weak activator of AhR. So he used the chemical scaffold of I3C to do a ‘virtual’ screen of a publicly-available database of millions of compounds to find those that were related to I3C but would bind to AhR with more strength. His team came up with 2,2?-aminophenyl indole (2AI) which is ten times more potent than I3C.
“2AI protected human retinal cells in culture from stress,” said Ramanathan. “And it also protected retinal cells in mice from light-mediated damage. We are very excited about the potential for 2AI and look forward to developing it further.” Ramanathan is also excited about the possibility of finding more potent versions of other naturally occurring molecules that show health benefits for age-related diseases. “You would have to eat an unreasonable amount of broccoli and other cruciferous vegetables to get enough of a protective effect to impact AMD,” he said. “This method allows us to capitalize on nature’s wisdom to find related molecules that can deliver therapeutic benefit.”