Characterization of Diabetic Retinopathy in Two Mouse Models and Response to a Single Injection of Anti-Vascular Endothelial Growth Factor

Tamar Azrad-Leibovich, Alon Zahavi, Moran Friedman Gohas, Myles Brookman, Orit Barinfeld, Orkun Muhsinoglu, Shalom Michowiz, Dror Fixler, Nitza Goldenberg-Cohen

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number324
JournalInternational Journal of Molecular Sciences
Issue number1
StatePublished - Jan 2023

Bibliographical note

Funding Information:
This study was partially supported by the ZANVYL AND ISABELLE KRIEGER FUND, Baltimore, Maryland, USA, and D-CURE, ISRAEL MINISTRY OF HEALTH AND ISRAEL SCIENTIFIC FOUNDATION, Jerusalem, Israel (grant number 3-0000-11401).

Publisher Copyright:
© 2022 by the authors.


  • anti-vascular endothelial growth factor
  • diabetic retinopathy
  • neovascularization
  • transgenic mice


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