Elovanoids counteract oligomeric β-Amyloid-induced gene expression and protect photoreceptors

The onset of neurodegenerative diseases activates inflammation that leads to progressive neuronal cell death and impairments in cognition (Alzheimer’s disease, AD) and sight (age-related macular degeneration, AMD). How neuroinflammation can be counteracted is not known. In AMD, amyloid β-peptide (Aβ) accumulates in subretinal drusen. In the 5xFAD retina, we found early functional deficiencies (ERG) without photoreceptor cell (PRC) death and identified early insufficiency in biosynthetic pathways of pro-homeostatic/neuroprotective mediators, neuroprotectin D1 (NPD1) and elovanoids (ELVs). To mimic an inflammatory milieu in wild-type (WT) mouse, we triggered retinal pigment epithelium (RPE) damage/PRC death by subretinally injected oligomeric β-Amyloid (OAβ) and observed that ELVs administration counteracted their effects, protecting these cells. In addition, ELVs prevented OAβ-induced changes in gene expression engaged in senescence, inflammation, autophagy, extracellular matrix remodeli...