LA JOLLA, CA—Many conditions that cause vision loss share a common feature: the gradual breakdown of the retina, the light-sensing tissue at the back of the eye. Although scientists know some of the structural changes that ensue as this damage progresses, less is understood about the molecular signals that shape how the retina copes with disease.
Now, a team at Scripps Research, in collaboration with UC San Diego and the Lowy Medical Research Institute, have found that a naturally occurring molecule called erucamide plays a role in how cells communicate in the retina. Their study, published in Nature Neuroscience on June 19, 2026, found that while erucamide levels drop as light-sensing cells known as photoreceptors begin to die, restoring the molecule activates cellular responses that support retinal stability. These findings suggest that erucamide may be part of a natural protective response in the retina, and could offer a new way to slow the progression of diseases that lead to vision loss.
"The retina doesn't simply deteriorate; in fact, it actively responds to injury," says senior author Martin Friedlander , a professor at Scripps Research. "Our work identifies erucamide as a signaling molecule that helps coordinate that response."
The retina depends on constant communication between neurons, glia, blood vessels and immune cells. This system, the neurovascular unit, keeps visual tissue functioning. But in diseases associated with loss of vision such as diabetic retinopathy, retinitis pigmentosa and age-related macular degeneration, that tight coordination wanes. Photoreceptors start dying, and eyesight fades.
The work from Friedlander's team builds on earlier observations that transplanted stem cell-derived retinal cells could slow degeneration long after the cells had disappeared, suggesting they were releasing protective signals that outlasted their own survival. This insight prompted the team to search for the specific molecules responsible.
Though it's long been recognized that fat-like compounds called lipids can act as signaling molecules in the body, many of these compounds haven't been carefully studied in the context of retinal disease. To search for overlooked players, the scientists used mass spectrometry-based metabolomics: a technique that measures many small molecules in tissue at once. The team applied this approach to several well-established preclinical models of retinal degeneration, searching for molecules that changed as disease progressed.
Among the many molecules detected, erucamide stood out. Its levels fell sharply as photoreceptors began to deteriorate, suggesting the decline may not be incidental.
"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 team then set out to determine whether restoring erucamide could affect the retinal degenerative process. Using porous silicon nanoparticles—tiny, engineered delivery vehicles designed to release molecules in a controlled way—the scientists reintroduced erucamide into the eye. Because erucamide is hydrophobic (meaning it doesn't dissolve well in water) and can form clumps when injected, the nanoparticles helped keep the molecule stable and evenly distributed.
Rather than acting directly on photoreceptors, erucamide activated a group of immune cells in the retina known as CD11b⁺ myeloid cells, which react to injury and support tissue health throughout the body. The team also identified a protein called TMEM19 that erucamide binds to; reducing TMEM19 levels prevented activation of these myeloid cells and blocked erucamide's protective effects.
Once stimulated, myeloid cells released signals associated with neurovascular stabilization, supporting both the nerve cells and the blood vessels that nourish them. While the effect wasn't an outright reversal of retinal damage, it slowed aspects of degeneration by preserving the structure and function of remaining tissue.
"Instead of targeting the photoreceptors themselves, erucamide appears to work by engaging the surrounding environment," explains first author Guoqin Wei, a staff scientist at Scripps Research who began working on this project as a postdoctoral research associate in Friedlander's lab seven years earlier. "That shift in perspective could be important for treating degenerative retinal diseases going forward."
Although the team's discovery offers a glimpse into how erucamide's effects happen at the molecular level, additional studies are needed to clarify the full pathway. Future work will focus on erucamide signaling in various retinal diseases, and whether targeting this pathway can provide meaningful benefits over time.
And since erucamide's hydrophobicity poses a formulation challenge—as most medicines for the eye are water-based—the scientists aim to improve how the molecule can be delivered as a therapy. They're also planning to test modified versions of erucamide to see whether they produce stronger or more stable effects, while also investigating whether related lipid molecules may be even more effective than erucamide at activating protective responses.
Still, the findings highlight a broader notion: that some molecules already present in the body may be harnessed to support tissue under stress. The early results point to a potential strategy for slowing retinal degeneration by strengthening the tissue's own response to damage.
"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."
In addition to Friedlander, Boger and Wei, authors of the study, " A fatty acid amide activates myeloid cells and improves neurovascular outcomes in retinal degeneration ," include Shreyosree Chatterjee, Daisuke Ogasawara, Katie Biscocho, Peter Westenskow, Junhua Wang, Helena Pham, Edith Aguilar, Jacob Robinson, Ayumi Usui-Ouchi, Gary Siuzdak and Benjamin Cravatt of Scripps Research; Qinglin Yang, Sanahan Vijayakumar, Ruhan Fan and Michael J. Sailor of UC San Diego; and Sarah Giles, Roberto Bonelli and Kevin Eade of the Lowy Medical Research Institute.
This work was supported by funding from the Lowy Medical Research Institute; the National Eye Institute (grants R01EY11254 and 5R24EY017540); the California Institute for Regenerative Medicine (grant TR1-01219); the National Science Foundation through the UC San Diego Materials Research Science and Engineering Center (grant DMR-2011924); the National Institutes of Health (grants 2R01AI132413, R35 GM130385, U01 CA235493 and U01 CA305256); the National Institute on Drug Abuse (grant DA015648), the San Diego Nanotechnology Infrastructure of UC San Diego, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (grant ECCS-2025752); and the Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship–Doctoral program (grant NSERC PGS-D).
About Scripps Research
Scripps Research is an independent, nonprofit biomedical research institute ranked one of the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr-Skaggs, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu .
