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Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice

Diabetic retinopathy (DR) is the leading cause of vision loss in working age adults. Understanding the retinal metabolic response to circulating high glucose levels in diabetic patients is critical for development of new therapeutics to treat DR. Measuring retinal metabolic function using the Seahor...

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Autores principales: Shosha, Esraa, Qin, Luke, Lemtalsi, Tahira, Zaidi, Syed A. H., Rojas, Modesto, Xu, Zhimin, Caldwell, Robert William, Caldwell, Ruth B., Fouda, Abdelrahman Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201036/
https://www.ncbi.nlm.nih.gov/pubmed/35722112
http://dx.doi.org/10.3389/fcvm.2022.900640
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author Shosha, Esraa
Qin, Luke
Lemtalsi, Tahira
Zaidi, Syed A. H.
Rojas, Modesto
Xu, Zhimin
Caldwell, Robert William
Caldwell, Ruth B.
Fouda, Abdelrahman Y.
author_facet Shosha, Esraa
Qin, Luke
Lemtalsi, Tahira
Zaidi, Syed A. H.
Rojas, Modesto
Xu, Zhimin
Caldwell, Robert William
Caldwell, Ruth B.
Fouda, Abdelrahman Y.
author_sort Shosha, Esraa
collection PubMed
description Diabetic retinopathy (DR) is the leading cause of vision loss in working age adults. Understanding the retinal metabolic response to circulating high glucose levels in diabetic patients is critical for development of new therapeutics to treat DR. Measuring retinal metabolic function using the Seahorse analyzer is a promising technique to investigate the effect of hyperglycemia on retinal glycolysis and mitochondrial respiration. Here, we analyzed the retinal metabolic function in young and old diabetic and control mice. We also compared the expression of key glycolytic enzymes between the two groups. The Seahorse XF analyzer was used to measure the metabolic function of retina explants from young and old type 1 diabetic Akita (Ins2(Akita)) mice and their control littermates. Rate-limiting glycolytic enzymes were analyzed in retina lysates from the two age groups by Western blotting. Retinas from young adult Akita mice showed a decreased glycolytic response as compared to control littermates. However, this was not observed in the older mice. Western blotting analysis showed decreased expression of the glycolytic enzyme PFKFB3 in the young Akita mice retinas. Measurement of the oxygen consumption rate showed no difference in retinal mitochondrial respiration between Akita and WT littermates under normal glucose conditions ex vivo despite mitochondrial fragmentation in the Akita retinas as examined by electron microscopy. However, Akita mice retinas showed decreased mitochondrial respiration under glucose-free conditions. In conclusion, diabetic retinas display a decreased glycolytic response during the early course of diabetes which is accompanied by a reduction in PFKFB3. Diabetic retinas exhibit decreased mitochondrial respiration under glucose deprivation.
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spelling pubmed-92010362022-06-17 Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice Shosha, Esraa Qin, Luke Lemtalsi, Tahira Zaidi, Syed A. H. Rojas, Modesto Xu, Zhimin Caldwell, Robert William Caldwell, Ruth B. Fouda, Abdelrahman Y. Front Cardiovasc Med Cardiovascular Medicine Diabetic retinopathy (DR) is the leading cause of vision loss in working age adults. Understanding the retinal metabolic response to circulating high glucose levels in diabetic patients is critical for development of new therapeutics to treat DR. Measuring retinal metabolic function using the Seahorse analyzer is a promising technique to investigate the effect of hyperglycemia on retinal glycolysis and mitochondrial respiration. Here, we analyzed the retinal metabolic function in young and old diabetic and control mice. We also compared the expression of key glycolytic enzymes between the two groups. The Seahorse XF analyzer was used to measure the metabolic function of retina explants from young and old type 1 diabetic Akita (Ins2(Akita)) mice and their control littermates. Rate-limiting glycolytic enzymes were analyzed in retina lysates from the two age groups by Western blotting. Retinas from young adult Akita mice showed a decreased glycolytic response as compared to control littermates. However, this was not observed in the older mice. Western blotting analysis showed decreased expression of the glycolytic enzyme PFKFB3 in the young Akita mice retinas. Measurement of the oxygen consumption rate showed no difference in retinal mitochondrial respiration between Akita and WT littermates under normal glucose conditions ex vivo despite mitochondrial fragmentation in the Akita retinas as examined by electron microscopy. However, Akita mice retinas showed decreased mitochondrial respiration under glucose-free conditions. In conclusion, diabetic retinas display a decreased glycolytic response during the early course of diabetes which is accompanied by a reduction in PFKFB3. Diabetic retinas exhibit decreased mitochondrial respiration under glucose deprivation. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201036/ /pubmed/35722112 http://dx.doi.org/10.3389/fcvm.2022.900640 Text en Copyright © 2022 Shosha, Qin, Lemtalsi, Zaidi, Rojas, Xu, Caldwell, Caldwell and Fouda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Shosha, Esraa
Qin, Luke
Lemtalsi, Tahira
Zaidi, Syed A. H.
Rojas, Modesto
Xu, Zhimin
Caldwell, Robert William
Caldwell, Ruth B.
Fouda, Abdelrahman Y.
Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice
title Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice
title_full Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice
title_fullStr Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice
title_full_unstemmed Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice
title_short Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice
title_sort investigation of retinal metabolic function in type 1 diabetic akita mice
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201036/
https://www.ncbi.nlm.nih.gov/pubmed/35722112
http://dx.doi.org/10.3389/fcvm.2022.900640
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