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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.900640/full |
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| author | Esraa Shosha Esraa Shosha Esraa Shosha Luke Qin Tahira Lemtalsi Tahira Lemtalsi Syed A. H. Zaidi Syed A. H. Zaidi Modesto Rojas Modesto Rojas Zhimin Xu Zhimin Xu Robert William Caldwell Robert William Caldwell Ruth B. Caldwell Ruth B. Caldwell Abdelrahman Y. Fouda Abdelrahman Y. Fouda |
| author_facet | Esraa Shosha Esraa Shosha Esraa Shosha Luke Qin Tahira Lemtalsi Tahira Lemtalsi Syed A. H. Zaidi Syed A. H. Zaidi Modesto Rojas Modesto Rojas Zhimin Xu Zhimin Xu Robert William Caldwell Robert William Caldwell Ruth B. Caldwell Ruth B. Caldwell Abdelrahman Y. Fouda Abdelrahman Y. Fouda |
| author_sort | Esraa Shosha |
| collection | DOAJ |
| 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 (Ins2Akita) 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. |
| first_indexed | 2024-12-11T18:16:57Z |
| format | Article |
| id | doaj.art-25b0ec4ab768404b8dea9721d36dfb40 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-11T18:16:57Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-25b0ec4ab768404b8dea9721d36dfb402022-12-22T00:55:23ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.900640900640Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita MiceEsraa Shosha0Esraa Shosha1Esraa Shosha2Luke Qin3Tahira Lemtalsi4Tahira Lemtalsi5Syed A. H. Zaidi6Syed A. H. Zaidi7Modesto Rojas8Modesto Rojas9Zhimin Xu10Zhimin Xu11Robert William Caldwell12Robert William Caldwell13Ruth B. Caldwell14Ruth B. Caldwell15Abdelrahman Y. Fouda16Abdelrahman Y. Fouda17Vascular Biology Center, Augusta University, Augusta, GA, United StatesDepartment of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Giza, EgyptUniversity of Arkansas for Medical Sciences, Little Rock, AR, United StatesVascular Biology Center, Augusta University, Augusta, GA, United StatesVascular Biology Center, Augusta University, Augusta, GA, United StatesCulver Vision Discovery Institute, Augusta University, Augusta, GA, United StatesVascular Biology Center, Augusta University, Augusta, GA, United StatesCulver Vision Discovery Institute, Augusta University, Augusta, GA, United StatesVascular Biology Center, Augusta University, Augusta, GA, United StatesCulver Vision Discovery Institute, Augusta University, Augusta, GA, United StatesVascular Biology Center, Augusta University, Augusta, GA, United StatesCulver Vision Discovery Institute, Augusta University, Augusta, GA, United StatesCulver Vision Discovery Institute, Augusta University, Augusta, GA, United StatesDepartment of Pharmacology and Toxicology, Augusta University, Augusta, GA, United StatesVascular Biology Center, Augusta University, Augusta, GA, United StatesCulver Vision Discovery Institute, Augusta University, Augusta, GA, United StatesDepartment of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Giza, EgyptUniversity of Arkansas for Medical Sciences, Little Rock, AR, United StatesDiabetic 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 (Ins2Akita) 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.https://www.frontiersin.org/articles/10.3389/fcvm.2022.900640/fulldiabetic retinopathyAkita micetype 1 diabetesretinal metabolic functionSeahorseglycolysis |
| spellingShingle | Esraa Shosha Esraa Shosha Esraa Shosha Luke Qin Tahira Lemtalsi Tahira Lemtalsi Syed A. H. Zaidi Syed A. H. Zaidi Modesto Rojas Modesto Rojas Zhimin Xu Zhimin Xu Robert William Caldwell Robert William Caldwell Ruth B. Caldwell Ruth B. Caldwell Abdelrahman Y. Fouda Abdelrahman Y. Fouda Investigation of Retinal Metabolic Function in Type 1 Diabetic Akita Mice Frontiers in Cardiovascular Medicine diabetic retinopathy Akita mice type 1 diabetes retinal metabolic function Seahorse glycolysis |
| 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 | diabetic retinopathy Akita mice type 1 diabetes retinal metabolic function Seahorse glycolysis |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.900640/full |
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