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Lack of the antioxidant enzyme methionine sulfoxide reductase A in mice impairs RPE phagocytosis and causes photoreceptor cone dysfunction
- Source :
- Redox Biology, Redox Biology, Elsevier, 2021, pp.101918. ⟨10.1016/j.redox.2021.101918⟩, Redox Biology, Vol 42, Iss, Pp 101918-(2021), Redox Biology, 2021, pp.101918. ⟨10.1016/j.redox.2021.101918⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- Methionine sulfoxide reductase A (MsrA) is a widely expressed antioxidant enzyme that counteracts oxidative protein damage and contributes to protein regulation by reversing oxidation of protein methionine residues. In retinal pigment epithelial (RPE) cells in culture, MsrA overexpression increases phagocytic capacity by supporting mitochondrial ATP production. Here, we show elevated retinal protein carbonylation indicative of oxidation, decreased RPE mitochondrial membrane potential, and attenuated RPE phagocytosis in msra−/− mice. Moreover, electroretinogram recordings reveal decreased light responses specifically of cone photoreceptors despite normal expression and localization of cone opsins. Impairment in msra−/− cone-driven responses is similar from 6 weeks to 13 months of age. These functional changes match dramatic decreases in lectin-labeled cone sheaths and reduction in cone arrestin in msra−/− mice. Strikingly, cone defects in light response and in lectin-labeled cone sheath are completely prevented by dark rearing. Together, our data show that msra−/− mice provide a novel small animal model of preventable cone-specific photoreceptor dysfunction that may have future utility in analysis of cone dystrophy disease mechanisms and testing therapeutic approaches aiming to alleviate cone defects.<br />Graphical abstract Image 1
- Subjects :
- 0301 basic medicine
Photoreceptors
Medicine (General)
RPE, retinal pigment epithelium
genetic structures
QH301-705.5
[SDV]Life Sciences [q-bio]
Clinical Biochemistry
Oxidative phosphorylation
medicine.disease_cause
Biochemistry
Antioxidants
Retina
MsrA, methionine sulfoxide reductase A
Mice
03 medical and health sciences
chemistry.chemical_compound
R5-920
0302 clinical medicine
Cone dystrophy
Phagocytosis
medicine
Animals
Electroretinogram, ERG
Biology (General)
Retinal pigment epithelium
Methionine
Chemistry
Organic Chemistry
MsrA
Retinal
medicine.disease
Mitochondria
3. Good health
Cell biology
[SDV] Life Sciences [q-bio]
030104 developmental biology
medicine.anatomical_structure
Oxidative stress
Methionine Sulfoxide Reductases
POS, photoreceptor outer segment fragments
sense organs
030217 neurology & neurosurgery
Research Paper
MSRA
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Database :
- OpenAIRE
- Journal :
- Redox Biology, Redox Biology, Elsevier, 2021, pp.101918. ⟨10.1016/j.redox.2021.101918⟩, Redox Biology, Vol 42, Iss, Pp 101918-(2021), Redox Biology, 2021, pp.101918. ⟨10.1016/j.redox.2021.101918⟩
- Accession number :
- edsair.doi.dedup.....77cd6ae99956edab0fe8511438559c03