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

Animals Lipofuscin Mice Reactive Oxygen Species Retinal Degeneration Retinal Pigment Epithelium Stargardt Disease
Age-related macular degeneration Lipofuscin Mouse model Pharmacological therapy Reactive oxygen species Retinal pigment epithelium Stargardt disease

Journal

Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159

Informations de publication

Date de publication:
03 2022
Historique:
received: 20 01 2022
revised: 17 02 2022
accepted: 22 02 2022
pubmed: 28 2 2022
medline: 6 4 2022
entrez: 27 2 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.freeradbiomed.2022.02.025 PMID: 35219849
pubmed: 35219849
pii: S0891-5849(22)00078-8
doi: 10.1016/j.freeradbiomed.2022.02.025
pii:
doi:

Substances chimiques

Lipofuscin 0
Reactive Oxygen Species 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

132-149

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Yuan Fang (Y)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.

Tatjana Taubitz (T)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.

Alexander V Tschulakow (AV)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; STZ Ocutox, Preclinical Drug Assessment, Hechingen, Germany.

Peter Heiduschka (P)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.

Grzegorz Szewczyk (G)

Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

Michael Burnet (M)

Synovo GmbH, Tuebingen, Germany.

Tobias Peters (T)

Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.

Antje Biesemeier (A)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.

Tadeusz Sarna (T)

Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

Ulrich Schraermeyer (U)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; STZ Ocutox, Preclinical Drug Assessment, Hechingen, Germany.

Sylvie Julien-Schraermeyer (S)

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; STZ Ocutox, Preclinical Drug Assessment, Hechingen, Germany. Electronic address: Sylvie.Julien@med.uni-tuebingen.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Removal of RPE lipofuscin results in rescue...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Lipofuscine › Removal of RPE lipofuscin results in rescue...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Removal of RPE lipofuscin results in rescue...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Removal of RPE lipofuscin results in rescue...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Dégénérescence de la rétine › Removal of RPE lipofuscin results in rescue...
questionsmedicales.fr › Organes des sens › Oeil › Rétine › Épithélium pigmentaire de la rétine › Removal of RPE lipofuscin results in rescue...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies héréditaires de l'oeil › Maladie de Stargardt › Removal of RPE lipofuscin results in rescue...