{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:15:34Z","timestamp":1767651334731,"version":"3.41.2"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T00:00:00Z","timestamp":1604793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GQ1422B"],"award-info":[{"award-number":["01GQ1422B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Age\u2010related macular degeneration (AMD) is the leading cause of blindness in older people in the developed world while Stargardt's disease (SD) is a juvenile macular degeneration and an orphan disease. Both diseases are untreatable and are marked by accumulation of lipofuscin advancing to progressive deterioration of the retinal pigment epithelium (RPE) and retina and subsequent vision loss till blindness. We discovered that a small molecule belonging to the tetrahydropyridoether class of compounds, soraprazan renamed remofuscin, is able to remove existing lipofuscin from the RPE. This study investigated the drug penetration, distribution, and elimination into the eyes of a mouse model for increased lipofuscinogenesis, following a single intravitreal injection. We measured the time course of concentrations of remofuscin in different eye tissues using high\u2010performance liquid chromatography combined with mass spectroscopy (HPLC\u2010MS). We also visualized the penetration and distribution of <jats:sup>3<\/jats:sup>H\u2010remofuscin in eye sections up to 20\u00a0weeks post\u2010injection using transmission electron microscopic (TEM) autoradiography. The distribution of silver grains revealed that remofuscin accumulated specifically in the RPE by binding to the RPE pigments (melanin, lipofuscin and melanolipofuscin) and that it was still detected after 20\u00a0weeks. Importantly, the melanosomes in choroidal melanocytes only rarely bind remofuscin emphasizing its potential to serve as an active ingredient in the RPE for the treatment of SD and dry AMD. In addition, our study highlights the importance of electron microscopic autoradiography as it is the only method able to show drug binding with a high intracellular resolution.<\/jats:p>","DOI":"10.1002\/prp2.683","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T06:43:44Z","timestamp":1604904224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Penetration, distribution, and elimination of remofuscin\/soraprazan in Stargardt mouse eyes following a single intravitreal injection using pharmacokinetics and transmission electron microscopic autoradiography: Implication for the local treatment of Stargardt\u2019s disease and dry age\u2010related macular degeneration"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-511X","authenticated-orcid":false,"given":"Sylvie","family":"Julien\u2010Schraermeyer","sequence":"first","affiliation":[{"name":"Division of Experimental Vitreoretinal Surgery Centre for Ophthalmology University of Tuebingen T\u00fcbingen Germany"},{"name":"STZ Ocutox \u2010 Preclinical Drug Assessment Hechingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Illing","sequence":"additional","affiliation":[{"name":"Division of Experimental Vitreoretinal Surgery Centre for Ophthalmology University of Tuebingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Tschulakow","sequence":"additional","affiliation":[{"name":"Division of Experimental Vitreoretinal Surgery Centre for Ophthalmology University of Tuebingen T\u00fcbingen Germany"},{"name":"STZ Ocutox \u2010 Preclinical Drug Assessment Hechingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatjana","family":"Taubitz","sequence":"additional","affiliation":[{"name":"Division of Experimental Vitreoretinal Surgery Centre for Ophthalmology University of Tuebingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamil","family":"Guezguez","sequence":"additional","affiliation":[{"name":"Synovo GmbH Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Burnet","sequence":"additional","affiliation":[{"name":"Synovo GmbH Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Schraermeyer","sequence":"additional","affiliation":[{"name":"Division of Experimental Vitreoretinal Surgery Centre for Ophthalmology University of Tuebingen T\u00fcbingen Germany"},{"name":"STZ Ocutox \u2010 Preclinical Drug Assessment Hechingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,8]]},"reference":[{"issue":"3","key":"e_1_2_10_2_1","first-page":"299","article-title":"Age\u2010related macular degeneration. 1. 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