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Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival and function in a mouse model of light damage (LD)-induced PR degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LD was induced by exposing mice to 4000\u00a0lx of light for 2\u20134\u00a0hours (h). IBU (100 or 200\u00a0mg\/kg) or vehicle was administered by daily intraperitoneal injection. Retinal structure and function were evaluated by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG). Cell death genes were analyzed at 24 and 72\u00a0h after LD using the Mouse Pan-Cell Death Pathway PCR Array (88 genes). The cellular location and protein expression of key necroptosis genes were assessed by immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Retinal outer nuclear layer (ONL) thickness in vehicle-injected LD animals was 8.7\u2009\u00b1\u20090.6% of retinas without LD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). In IBU 200\u00a0mg\/kg treated mice, central ONL thickness was 74.9\u2009\u00b1\u20097.7% of untreated retinas (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). A-wave and b-wave ERG amplitudes were significantly preserved in IBU-treated animals. IBU significantly inhibited retinal inflammation. Twenty-four hour after LD, retinal mRNA expression for the inflammatory-factors tumor necrosis factor (\n                      <jats:italic>Tnf<\/jats:italic>\n                      ), interleukin-1 beta (\n                      <jats:italic>Il1B<\/jats:italic>\n                      ), and C-C motif chemokine ligand 2 (\n                      <jats:italic>Ccl2<\/jats:italic>\n                      ) increased by 10-, 17-, and 533-fold, respectively; in IBU-treated animals, the expression levels of these inflammatory factors were not significantly different from no-LD controls. Expression of key necroptosis genes, including\n                      <jats:italic>Ripk3<\/jats:italic>\n                      and\n                      <jats:italic>Mlkl<\/jats:italic>\n                      , were upregulated in LD vehicle-treated mice, but dramatically reduced to near no LD levels in LD IBU-treated mice. Microglia activation and MLKL protein upregulation were observed primarily in photoreceptors 12\u00a0h after LD, as assessed by immunohistochemistry. IBU reduced the upregulation of MLKL protein and microglia migration in the ONL and outer plexiform layer (OPL) of treated retinas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systemic administration of the anti-inflammatory drug IBU partially protected mouse retinas from light-induced photochemical damage and inhibited both inflammation and the necroptosis cell death pathways. Our results suggest that NSAIDs may provide a promising therapeutic approach for treatment of the human retinal degenerative diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-024-03329-8","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T02:56:25Z","timestamp":1738032985000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration"],"prefix":"10.1186","volume":"22","author":[{"given":"Ping-Wu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-He","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Vats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey J.","family":"Keuthan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Berlinicke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Esumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elia J","family":"Duh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"Zack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"issue":"16","key":"3329_CR1","doi-asserted-by":"publisher","first-page":"5089","DOI":"10.3390\/molecules27165089","volume":"27","author":"M Fabre","year":"2022","unstructured":"Fabre M, Mateo L, Lamaa D, Baillif S, Pag\u00e8s G, Demange L, Ronco C, Benhida R. 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