PuSH - Publikationsserver des Helmholtz Zentrums München

Ayten, M.* ; Díaz-Lezama, N.* ; Ghanawi, H.* ; Haffelder, F.C.* ; Kajtna, J.* ; Straub, T.* ; Borsò, M.* ; Imhof, A.* ; Hauck, S.M. ; Koch, S.F.*

Metabolic plasticity in a Pde6bSTOP/STOP retinitis pigmentosa mouse model following rescue.

Mol. Metab. 88:101994 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor degeneration, leading to vision loss. The best hope for a cure for RP lies in gene therapy. However, given that RP patients are most often diagnosed in the midst of ongoing photoreceptor degeneration, it is important to determine how the retinal proteome changes as RP disease progresses, and to identify which changes can be prevented, halted, or reversed by gene therapy. Here, we used our Pde6b-deficient RP gene therapy mouse model and demonstrated that Pde6b gene restoration led to a novel form of homeostatic plasticity in rod phototransduction which functionally compensates for the decreased number of rods. By profiling protein levels of metabolic genes and measuring metabolites, we observed an upregulation of proteins associated with oxidative phosphorylation in mutant and treated photoreceptors. Thus, the metabolic demands of the retina differ in our Pde6b-deficient RP mouse model and are not rescued by gene therapy treatment. These findings provide novel insights into features of both RP disease progression and long-term rescue with gene therapy.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Gene Therapy ; Inflammation ; Metabolism ; Oxphos ; Phototransduction ; Proteomics ; Retina ; Retinal Plasticity ; Retinitis Pigmentosa; Muller Cells; Cone Death; Proteomics; Glucose
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 88, Heft: , Seiten: , Artikelnummer: 101994 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Förderungen Bayerische Forschungsstiftung
Daimler and Benz Foundation
German Research Foundation