Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor
In this study, we characterized diabetic retinopathy in two mouse models and the response to anti-vascular endothelial growth factor (VEGF) injection. The study was conducted in 58 transgenic, non-obese diabetic (NOD) mice with spontaneous type 1 diabetes (n = 30, DMT1-NOD) or chemically induced (n...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/324 |
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| author | Tamar Azrad-Leibovich Alon Zahavi Moran Friedman Gohas Myles Brookman Orit Barinfeld Orkun Muhsinoglu Shalom Michowiz Dror Fixler Nitza Goldenberg-Cohen |
| author_facet | Tamar Azrad-Leibovich Alon Zahavi Moran Friedman Gohas Myles Brookman Orit Barinfeld Orkun Muhsinoglu Shalom Michowiz Dror Fixler Nitza Goldenberg-Cohen |
| author_sort | Tamar Azrad-Leibovich |
| collection | DOAJ |
| description | In this study, we characterized diabetic retinopathy in two mouse models and the response to anti-vascular endothelial growth factor (VEGF) injection. The study was conducted in 58 transgenic, non-obese diabetic (NOD) mice with spontaneous type 1 diabetes (n = 30, DMT1-NOD) or chemically induced (n = 28, streptozotocin, STZ-NOD) type 1 diabetes and 20 transgenic db/db mice with type 2 diabetes (DMT2-db/db); 30 NOD and 8 wild-type mice served as controls. Mice were examined at 21 days for vasculopathy, retinal thickness, and expression of genes involved in oxidative stress, angiogenesis, gliosis, and diabetes. The right eye was histologically examined one week after injection of bevacizumab, ranibizumab, saline, or no treatment. Flat mounts revealed microaneurysms and one apparent area of tufts of neovascularization in the diabetic retina. Immunostaining revealed activation of Müller glia and prominent Müller cells. Mean retinal thickness was greater in diabetic mice. RAGE increased and GFAP decreased in DMT1-NOD mice; GFAP and SOX-9 mildly increased in db/db mice. Anti-VEGF treatment led to reduced retinal thickness. Retinas showed vasculopathy and edema in DMT1-NOD and DMT2-db/db mice and activation of Müller glia in DMT1-NOD mice, with some response to anti-VEGF treatment. Given the similarity of diabetic retinopathy in mice and humans, comparisons of type 1 and type 2 diabetic mouse models may assist in the development of new treatment modalities. |
| first_indexed | 2024-03-11T10:00:04Z |
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| id | doaj.art-a3994d8b5c6f4f6288620e920894fca9 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T10:00:04Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3994d8b5c6f4f6288620e920894fca92023-11-16T15:31:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124132410.3390/ijms24010324Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth FactorTamar Azrad-Leibovich0Alon Zahavi1Moran Friedman Gohas2Myles Brookman3Orit Barinfeld4Orkun Muhsinoglu5Shalom Michowiz6Dror Fixler7Nitza Goldenberg-Cohen8Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelKrieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelKrieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, IsraelKrieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, IsraelDepartment of Neurosurgery, Rabin Medical Center—Beilinson Hospital, Petach Tikva 4941492, IsraelFaculty of Engineering and Institute of Nanotechonology and Advanced Materials, Bar Ilan University, Ramat Gan 5200100, IsraelKrieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, IsraelIn this study, we characterized diabetic retinopathy in two mouse models and the response to anti-vascular endothelial growth factor (VEGF) injection. The study was conducted in 58 transgenic, non-obese diabetic (NOD) mice with spontaneous type 1 diabetes (n = 30, DMT1-NOD) or chemically induced (n = 28, streptozotocin, STZ-NOD) type 1 diabetes and 20 transgenic db/db mice with type 2 diabetes (DMT2-db/db); 30 NOD and 8 wild-type mice served as controls. Mice were examined at 21 days for vasculopathy, retinal thickness, and expression of genes involved in oxidative stress, angiogenesis, gliosis, and diabetes. The right eye was histologically examined one week after injection of bevacizumab, ranibizumab, saline, or no treatment. Flat mounts revealed microaneurysms and one apparent area of tufts of neovascularization in the diabetic retina. Immunostaining revealed activation of Müller glia and prominent Müller cells. Mean retinal thickness was greater in diabetic mice. RAGE increased and GFAP decreased in DMT1-NOD mice; GFAP and SOX-9 mildly increased in db/db mice. Anti-VEGF treatment led to reduced retinal thickness. Retinas showed vasculopathy and edema in DMT1-NOD and DMT2-db/db mice and activation of Müller glia in DMT1-NOD mice, with some response to anti-VEGF treatment. Given the similarity of diabetic retinopathy in mice and humans, comparisons of type 1 and type 2 diabetic mouse models may assist in the development of new treatment modalities.https://www.mdpi.com/1422-0067/24/1/324diabetic retinopathyanti-vascular endothelial growth factorneovascularizationtransgenic mice |
| spellingShingle | Tamar Azrad-Leibovich Alon Zahavi Moran Friedman Gohas Myles Brookman Orit Barinfeld Orkun Muhsinoglu Shalom Michowiz Dror Fixler Nitza Goldenberg-Cohen Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor International Journal of Molecular Sciences diabetic retinopathy anti-vascular endothelial growth factor neovascularization transgenic mice |
| title | Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor |
| title_full | Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor |
| title_fullStr | Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor |
| title_full_unstemmed | Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor |
| title_short | Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor |
| title_sort | characterization of diabetic retinopathy in two mouse models and response to a single injection of anti vascular endothelial growth factor |
| topic | diabetic retinopathy anti-vascular endothelial growth factor neovascularization transgenic mice |
| url | https://www.mdpi.com/1422-0067/24/1/324 |
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