Development of a zebrafish screening model for diabetic retinopathy induced by hyperglycemia: Reproducibility verification in animal model

Biomed Pharmacother. 2021 Mar:135:111201. doi: 10.1016/j.biopha.2020.111201. Epub 2021 Feb 1.

Abstract

This study aimed at creating a zebrafish screening model for diabetic retinopathy, and evaluated the effects of aflibercept, which is being used to treated diabetic retinopathy. A morphological change occurred at 160 mM of glucose. The survival and hatching rate decreased in a dose-dependent manner. In the 130 mM glucose group, the retinal vessel diameter was more than double that in the normal group. The zebrafish embryo morphology changed in 200 μg/mL and 400 μg/mL at aflibercept. The survival and hatching rate decrease at 400 μg/mL. Aflibercept 100 μg/mL was a nontoxic and effective dose for the zebrafish diabetic retinopathy model. The expression of diabetic retinopathy inflammatory markers was increased in hyperglycemia. But the inflammation was improved by aflibercept in the zebrafish eye. In a zebrafish diabetic retinopathy model, the diameters of retinal vessels were reduced after treatment with aflibercept, and molecular biological and histopathological efficacy was confirmed. This model can serve for screening of new drug candidates for treatment of in diabetic retinopathy.

Keywords: Diabetic retinopathy; Eye; Inflammation; Zebrafish.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Animals, Genetically Modified
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / etiology*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Disease Models, Animal
  • Glucose*
  • Hyperglycemia / chemically induced
  • Hyperglycemia / complications*
  • Inflammation Mediators / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / pharmacology
  • Retinal Neovascularization*
  • Retinal Vessels / drug effects
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*
  • Zebrafish

Substances

  • Angiogenesis Inhibitors
  • Cytokines
  • Inflammation Mediators
  • Recombinant Fusion Proteins
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor
  • Glucose