Removal of RPE lipofuscin results in rescue from retinal degeneration in a mouse model of advanced Stargardt disease: Role of reactive oxygen species.
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| Abstract |
Accumulation of lipofuscin in the retinal pigment epithelium (RPE) is a hallmark of aging and is associated with retinal degeneration encountered in age-related macular degeneration (AMD) and Stargardt disease (SD). Currently, treatment for lipofuscin-induced retinal degeneration is unavailable. Here, we report that Remofuscin (INN: soraprazan, a tetrahydropyridoether small molecule) reverses lipofuscin accumulation in aged primary human RPE cells and is non-cytotoxic in aged SD mouse RPE cells in vitro. In addition, we show that the removal of lipofuscin after a single intravitreal injection of Remofuscin results in a rescue from retinal degeneration in a mouse model of advanced SD which is even accompanied by an amelioration of the retinal dysfunction. Finally, we demonstrate that the mechanism causing lipofuscinolysis may involve the reactive oxygen species generated via the presence of Remofuscin. These data suggest a possible therapeutic approach to untreatable lipofuscin-mediated diseases like AMD, SD and lipofuscinopathies in neurodegenerative diseases.
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| Authors | Yuan Fang, Tatjana Taubitz, Alexander V Tschulakow, Peter Heiduschka, Grzegorz Szewczyk, Michael Burnet, Tobias Peters, Antje Biesemeier, Tadeusz Sarna, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer |
| Journal | Free radical biology & medicine (Free Radic Biol Med) Vol. 182 Pg. 132-149 (03 2022) ISSN: 1873-4596 [Electronic] United States |
| PMID | 35219849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. |
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