{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:30:25Z","timestamp":1781105425359,"version":"3.54.1"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"48","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY005121"],"award-info":[{"award-number":["R01 EY005121"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,11,26]]},"abstract":"<jats:p>\n                    The onset of neurodegenerative diseases activates inflammation that leads to progressive neuronal cell death and impairments in cognition (Alzheimer\u2019s disease) and sight (age-related macular degeneration [AMD]). How neuroinflammation can be counteracted is not known. In AMD, amyloid \u03b2-peptide (A\u03b2) 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 prohomeostatic\/neuroprotective mediators neuroprotectin D1 (NPD1) and elovanoids (ELVs). To mimic an inflammatory milieu in wild-type mouse, we triggered retinal pigment epithelium (RPE) damage\/PRC death by subretinally injected oligomeric \u03b2-amyloid (OA\u03b2) and observed that ELVs administration counteracted their effects, protecting these cells. In addition, ELVs prevented OA\u03b2-induced changes in gene expression engaged in senescence, inflammation, autophagy, extracellular matrix remodeling, and AMD. Moreover, as OA\u03b2 targets the RPE, we used primary human RPE cell cultures and demonstrated that OA\u03b2 caused cell damage, while ELVs protected and restored gene expression as in mouse. Our data show OA\u03b2 activates senescence as reflected by enhanced expression of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    , MMP1, p53, p21, p27, and Il-6, and of senescence-associated phenotype secretome, followed by RPE and PRC demise, and that ELVs 32 and 34 blunt these events and elicit protection. In addition, ELVs counteracted OA\u03b2-induced expression of genes engaged in AMD, autophagy, and extracellular matrix remodeling. Overall, our data uncovered that ELVs downplay OA\u03b2-senescence program induction and inflammatory transcriptional events and protect RPE cells and PRC, and therefore have potential as a possible therapeutic avenue for AMD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1912959116","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T20:29:22Z","timestamp":1573504162000},"page":"24317-24325","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["Elovanoids counteract oligomeric \u03b2-amyloid-induced gene expression and protect photoreceptors"],"prefix":"10.1073","volume":"116","author":[{"given":"Khanh V.","family":"Do","sequence":"first","affiliation":[{"name":"Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Audrey I.","family":"Kautzmann","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bokkyoo","family":"Jun","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Nshimiyimana","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089-1661"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089-1661"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-4446","authenticated-orcid":false,"given":"Nicos A.","family":"Petasis","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089-1661"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas G.","family":"Bazan","sequence":"additional","affiliation":[{"name":"Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.tins.2006.03.005","article-title":"Cell survival matters: Docosahexaenoic acid signaling, neuroprotection and photoreceptors","volume":"29","author":"Bazan N. 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