TY - JOUR
T1 - Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor
AU - Azrad-Leibovich, Tamar
AU - Zahavi, Alon
AU - Gohas, Moran Friedman
AU - Brookman, Myles
AU - Barinfeld, Orit
AU - Muhsinoglu, Orkun
AU - Michowiz, Shalom
AU - Fixler, Dror
AU - Goldenberg-Cohen, Nitza
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - anti-vascular endothelial growth factor
KW - diabetic retinopathy
KW - neovascularization
KW - transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=85145964431&partnerID=8YFLogxK
U2 - 10.3390/ijms24010324
DO - 10.3390/ijms24010324
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C2 - 36613769
AN - SCOPUS:85145964431
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 1
M1 - 324
ER -