Researchers from the Washington University School of Medicine, St. Louis, have presented a novel strategy for preventing – or slowing down – age-related macular degeneration (AMD).
Their study set out to investigate the role of apolipoprotein M (ApoM) – a blood protein which carries the signaling molecule sphingosine-1-phosphate (S1P) – in AMD, with a focus on the early and intermediate disease stages.
The researchers found that AMD patients have significantly lower levels of circulating ApoM. Using mouse models that mimic dry AMD by disrupting cholesterol handling in photoreceptors, they demonstrated that boosting ApoM levels – via plasma transfer from ApoM-overexpressing mice – could improve retinal pigment epithelium (RPE) function and reduce lipid accumulation in the RPE.
Importantly, the protective effects of ApoM required its ability to bind S1P and activate a specific receptor on RPE cells, called S1P receptor 3 (S1PR3). This pathway didn’t work if either the S1P binding was disrupted or the receptor was missing. The team also showed that ApoM-S1P doesn't work by promoting cholesterol efflux (as previously thought), but rather by stimulating the RPE’s lysosomal system to break down lipids more effectively.
Further experiments confirmed that when this lysosomal function was knocked out, ApoM could no longer provide benefit – pinpointing this lipid degradation pathway as essential to the effect. The findings open the door to a potential therapy that could slow or prevent early AMD progression by improving the RPE’s ability to clear harmful lipids before vision is affected.
