{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:43:11Z","timestamp":1790376191637,"version":"4.1.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 (Abca4)\u2212\/\u2212 retinol dehydrogenase 8 (Rdh8)\u2212\/\u2212 double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2\u2212\/\u2212Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2\u2212\/\u2212Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice as compared with Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8, Ccl2, and Cxcl10. To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-\u03baB signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H2O2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration.<\/jats:p>","DOI":"10.4049\/jimmunol.1701573","type":"journal-article","created":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T13:55:15Z","timestamp":1522418115000},"page":"3128-3141","source":"Crossref","is-referenced-by-count":64,"title":["Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration"],"prefix":"10.1093","volume":"200","author":[{"given":"Tanu","family":"Parmar","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul M","family":"Parmar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Perusek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Georges","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology , Kobe, Hyogo 650-0047,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology , Kobe, Hyogo 650-0047,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Crabb","sequence":"additional","affiliation":[{"name":"Cole Eye Institute , Cleveland Clinic, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology , Kobe, Hyogo 650-0047,","place":["Japan"]},{"name":"Department of Pharmacology, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"key":"2025030610144995900_r1","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1167\/iovs.09-5073","article-title":"Altered expression of metallothionein-I and -II and their receptor megalin in inherited photoreceptor degeneration","volume":"51","author":"Wunderlich","year":"2010","journal-title":"Invest. 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