Gene expression mapping of eye after adipocyte depletion

Here we identify an adipose–retina axis that controls the enzymatic fate of docosahexaenoic acid (DHA), rather than its abundance. Genetic depletion of adipocytes causes visual dysfunction and photoreceptor degeneration despite increased retinal DHA, revealing a failure of lipid routing.

In mice and humans, loss of adipose-derived signals suppresses the DHA-oxygenating enzyme ALOX15 in the retinal pigment epithelium (RPE), limiting production of the pro-resolving mediator neuroprotectin D1 (NPD1). NPD1 promotes lipophagy-mediated clearance of photoreceptor outer-segment membranes through adenylate and purine remodeling, and its loss drives lipid accumulation and degeneration. Restoring adipokine signaling, or supplementing NPD1, improves RPE function, retinal structure, and vision in vivo.