A team at Scripps Research, in collaboration with UC San Diego and the Lowy Medical Research Institute, announced on June 22 that a naturally occurring molecule called erucamide may help slow progressive retinal degeneration. Their study, published in Nature Neuroscience on June 19, found that while erucamide levels drop as light-sensing photoreceptor cells begin to die, restoring the molecule activates cellular responses that support retinal stability.
The retina relies on communication between neurons, glia, blood vessels, and immune cells—a system known as the neurovascular unit—to maintain visual function. In diseases such as diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration, this coordination weakens and photoreceptors start dying.
Friedlander's team built on earlier findings suggesting transplanted stem cell-derived retinal cells could slow degeneration even after disappearing from the tissue. This led researchers to search for specific protective molecules using mass spectrometry-based metabolomics. Among many compounds detected during studies of preclinical models of retinal degeneration, erucamide stood out due to its sharp decline as disease progressed.
"That was a pivotal moment for us," recalls co-author Dale Boger, the Richard and Alice Cramer Professor of Chemistry at Scripps Research. "It raised the possibility that erucamide could be influencing how tissue responds and wasn't just changing as a consequence of disease."
The scientists reintroduced erucamide into the eye using porous silicon nanoparticles designed for controlled release. Rather than acting directly on photoreceptors, erucamide activated CD11b⁺ myeloid immune cells in the retina. The team also identified TMEM19 as a protein target; reducing TMEM19 prevented activation of these myeloid cells and blocked protective effects.
First author Guoqin Wei said, "Instead of targeting the photoreceptors themselves, erucamide appears to work by engaging the surrounding environment... That shift in perspective could be important for treating degenerative retinal diseases going forward." While not reversing damage outright, stimulating myeloid cells released signals associated with neurovascular stabilization—helping preserve structure and function of remaining tissue.
Further research is planned to clarify how erucamide signaling works across different diseases and whether modified versions or related lipids might offer stronger benefits. Scientists are also working to improve delivery methods given challenges posed by erucamide's hydrophobicity.
"The goal is to reinforce a signal that's already present," notes Friedlander. "If we can learn how to modulate that response carefully, it could offer a new path for slowing the progression of retinal diseases where treatment options remain limited."
