{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:27:17Z","timestamp":1776209237668,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["(EY024091, EY012951, S10OD028637"],"award-info":[{"award-number":["(EY024091, EY012951, S10OD028637"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Department of Ophthalmology Columbia University"],"award-info":[{"award-number":["Department of Ophthalmology Columbia University"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Ophthalmol."],"abstract":"Aim<\/jats:title>Iron dysregulation in conjunction with other disease processes may exacerbate retinal degeneration. We employed models of iron overload and iron chelation to explore the interactions between iron-catalyzed oxidation and photoreactive bisretinoid lipofuscin.<\/jats:p><\/jats:sec>Methods<\/jats:title>The mice were injected intravitreally with ferric ammonium citrate (FAC) or were treated using the iron chelator deferiprone (DFP) from birth to 2\u00a0months of age. Short-wavelength fundus autofluorescence (SW-AF) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired. The bisretinoid levels were quantified using ultra performance liquid chromatography (UPLC) and in vivo<\/jats:italic> through quantitative fundus autofluorescence (qAF). In histologic sections, the photoreceptor cell viability was assessed by measuring the thickness of the outer nuclear layer (ONL).<\/jats:p><\/jats:sec>Results<\/jats:title>The levels of bisretinoids, all-trans<\/jats:italic>-retinal dimers, and A2PE were significantly increased in the FAC-injected eyes of C57BL\/6J mice. Seven days after FAC injection, hyperautofluorescent foci were visible in fundus autofluorescence (488\u00a0nm) images, and in SD-OCT scans, aberrant hyperreflectivity was present in the outer retina and ONL thinning was observed. In FAC-injected Abca4\u2013\/\u2013<\/jats:sup><\/jats:italic> mice with pronounced RPE bisretinoid lipofuscin accumulation, the hyperautofluorescent puncta were more abundant than in the wild-type mice, and the extent of ONL thinning was greater. Conversely, the intravitreal injection of FAC in Mertk\u2013\/\u2013<\/jats:sup><\/jats:italic> mice led to a more modest increase in A2PE after 2 days. In contrast to the effect of iron accumulation, chelation with DFP resulted in significantly increased levels of A2E and A2-GPE and qAF due to the reduced iron-catalyzed oxidation of bisretinoids. In Mertk\u2013\/\u2013<\/jats:sup><\/jats:italic> mice, the A2E level was significantly lower and the ONL area was smaller than in DFP-treated mice. DFP chelation did not impair the visual cycle in BALB\/cJ mice.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Iron accumulation was associated with progressive impairment in photoreceptor cells that was associated with the increased formation of a bisretinoid species known to form in photoreceptor outer segments as a precursor to A2E. Additionally, disease features such as the development of hyperautofluorescence puncta in fundus AF images, hyperreflectivity in the outer retina of SD-OCT scans, and ONL thinning were more pronounced when iron was delivered to Abca4\u2013\/\u2013<\/jats:sup><\/jats:italic> mice with a greater propensity for bisretinoid formation. Higher bisretinoid levels and enhanced qAF are indicative of lesser bisretinoid loss due to oxidation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fopht.2023.1305864","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T04:42:12Z","timestamp":1703220132000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Iron overload and chelation modulates bisretinoid levels in the retina"],"prefix":"10.3389","volume":"3","author":[{"given":"Jin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Montenegro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josh 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