The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases.
Warburg effect
aerobic glycolysis
lactate dehydrogenases
photoreceptors
retina
Journal
PNAS nexus
ISSN: 2752-6542
Titre abrégé: PNAS Nexus
Pays: England
ID NLM: 9918367777906676
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
02
09
2022
revised:
28
01
2023
accepted:
31
01
2023
entrez:
10
3
2023
pubmed:
11
3
2023
medline:
11
3
2023
Statut:
epublish
Résumé
The postmitotic retina is highly metabolic and the photoreceptors depend on aerobic glycolysis for an energy source and cellular anabolic activities. Lactate dehydrogenase A (LDHA) is a key enzyme in aerobic glycolysis, which converts pyruvate to lactate. Here we show that cell-type-specific actively translating mRNA purification by translating ribosome affinity purification shows a predominant expression of LDHA in rods and cones and LDHB in the retinal pigment epithelium and Müller cells. We show that genetic ablation of LDHA in the retina resulted in diminished visual function, loss of structure, and a loss of dorsal-ventral patterning of the cone-opsin gradient. Loss of LDHA in the retina resulted in increased glucose availability, promoted oxidative phosphorylation, and upregulated the expression of glutamine synthetase (GS), a neuron survival factor. However, lacking LDHA in Müller cells does not affect visual function in mice. Glucose shortage is associated with retinal diseases, such as age-related macular degeneration (AMD), and regulating the levels of LDHA may have therapeutic relevance. These data demonstrate the unique and unexplored roles of LDHA in the maintenance of a healthy retina.
Identifiants
pubmed: 36896135
doi: 10.1093/pnasnexus/pgad038
pii: pgad038
pmc: PMC9991461
doi:
Types de publication
Journal Article
Langues
eng
Pagination
pgad038Subventions
Organisme : NEI NIH HHS
ID : P30 EY021725
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.
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