Data from: 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 remodeling and
AMD. Moreover, since OAβ target the RPE, we used primary human RPE cell
cultures and demonstrated that OAβ caused cell damage, while ELVs
protected and restored gene expression as in mouse. Our data show OAβ
activates senescence as reflected by enhanced expression of p16INK4a,
MMP1, p53, p21, p27 and Il-6 and of senescence-associated secretory
phenotype (SASP) secretome, followed by RPE and PRC demise and that
elovanoids 32 and 34 blunt these events and elicits protection. In
addition, ELVs counteracted OAβ-induced expression of genes engaged in
AMD, autophagy and extracellular matrix (ECM) remodeling. Overall, our
data uncovered that ELVs downplay OAβ-senescence program induction and
inflammatory transcriptional events and protect RPE cells and PRC, and
therefore have potential as a possible therapeutic avenue for AMD.