A molecular pathway involving apolipoprotein M (ApoM) may help prevent or slow the progression of age-related macular degeneration (AMD), according to a study recently published in Nature Communications. The findings suggest that ApoM supports lysosomal lipid clearance in retinal pigment epithelium (RPE) cells through sphingosine-1-phosphate (S1P) signaling, potentially offering a new early-stage therapeutic target for AMD.

Using human plasma samples, researchers from Washington University School of Medicine in St. Louis found that individuals with AMD had significantly lower levels of circulating ApoM than controls. In AMD mouse models, systemic ApoM administration reduced lipotoxicity and restored RPE function. These effects were dependent on S1P and its receptor S1PR3, suggesting that ApoM exerts its protective effect through S1P-mediated lysosomal lipid catabolism. ApoM had no therapeutic effect in mice lacking RPE-specific lysosomal acid lipase, indicating that its benefits rely on intact lipid degradation pathways.

The research provides additional evidence linking dysregulated cholesterol metabolism with AMD pathogenesis. ApoM’s role in lipid processing has also been implicated in cardiovascular disease, and the current findings reinforce the idea that systemic metabolic dysfunction may contribute to retinal degeneration.

ApoM-based interventions could differ from existing AMD treatments, such as complement inhibitors, which target later stages of disease. The ability to support lysosomal function and lipid clearance in the RPE may offer earlier intervention before irreversible retinal damage occurs.

Commercial development efforts are underway, with Mobius Scientific exploring ApoM-related therapies. Retina specialists may eventually see ApoM emerge as a biomarker or treatment component for AMD, though no clinical trials in humans have yet begun. Senior authors Rajendra S. Apte, MD, PhD, and Ali Javaheri, MD, PhD of Washington University School of Medicine, disclosed intellectual property licensed to Mobius Scientific and serve as advisors to the company. RP