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The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases

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 activel...

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Autores principales: Rajala, Ammaji, Bhat, Mohd A, Teel, Kenneth, Gopinadhan Nair, Gopa Kumar, Purcell, Lindsey, Rajala, Raju V S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9991461/
https://www.ncbi.nlm.nih.gov/pubmed/36896135
http://dx.doi.org/10.1093/pnasnexus/pgad038
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author Rajala, Ammaji
Bhat, Mohd A
Teel, Kenneth
Gopinadhan Nair, Gopa Kumar
Purcell, Lindsey
Rajala, Raju V S
author_facet Rajala, Ammaji
Bhat, Mohd A
Teel, Kenneth
Gopinadhan Nair, Gopa Kumar
Purcell, Lindsey
Rajala, Raju V S
author_sort Rajala, Ammaji
collection PubMed
description 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.
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spelling pubmed-99914612023-03-08 The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases Rajala, Ammaji Bhat, Mohd A Teel, Kenneth Gopinadhan Nair, Gopa Kumar Purcell, Lindsey Rajala, Raju V S PNAS Nexus Biological, Health, and Medical Sciences 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. Oxford University Press 2023-02-03 /pmc/articles/PMC9991461/ /pubmed/36896135 http://dx.doi.org/10.1093/pnasnexus/pgad038 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biological, Health, and Medical Sciences
Rajala, Ammaji
Bhat, Mohd A
Teel, Kenneth
Gopinadhan Nair, Gopa Kumar
Purcell, Lindsey
Rajala, Raju V S
The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases
title The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases
title_full The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases
title_fullStr The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases
title_full_unstemmed The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases
title_short The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases
title_sort function of lactate dehydrogenase a in retinal neurons: implications to retinal degenerative diseases
topic Biological, Health, and Medical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9991461/
https://www.ncbi.nlm.nih.gov/pubmed/36896135
http://dx.doi.org/10.1093/pnasnexus/pgad038
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