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Removal of RPE lipofuscin results in rescue from retinal degeneration in a mouse model of advanced Stargardt disease: Role of reactive oxygen species

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
Source :
Free Radical Biology and Medicine. 182:132-149
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

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.

Details

ISSN :
08915849
Volume :
182
Database :
OpenAIRE
Journal :
Free Radical Biology and Medicine
Accession number :
edsair.doi.dedup.....1d83cab6b21ba4299447158da783a3f4