Development of a zebrafish screening model for diabetic retinopathy induced by hyperglycemia: Reproducibility
1Inje University Busan Paik Hospital, Department of Ophthalmology. 81, Jinsa-ro 83beon-gil, Busanjin-gu, Busan, South Korea.
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.
Insights
Researchers developed a zebrafish model for diabetic retinopathy, confirming its effectiveness in evaluating treatments like aflibercept. This model aids in screening new drugs for diabetic eye disease.
Area of Science:
- Ophthalmology
- Genetics
- Pharmacology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- Current treatments for DR have limitations.
- A need exists for novel therapeutic strategies and screening models.
Purpose of the Study:
- To establish a zebrafish model for screening diabetic retinopathy (DR) treatments.
- To evaluate the efficacy of aflibercept in this zebrafish model.
- To investigate the effects of hyperglycemia and aflibercept on zebrafish retinal vasculature and inflammation.
Main Methods:
- Zebrafish embryos were exposed to varying glucose concentrations to induce diabetic conditions.
- Morphological changes, survival, and hatching rates were assessed.
- Retinal vessel diameter was measured using microscopy.
- Inflammatory markers were analyzed.
- Aflibercept treatment effects were evaluated at different concentrations.
Main Results:
- Hyperglycemia (160 mM glucose) induced morphological changes and reduced survival/hatching rates in zebrafish.
- Retinal vessel diameter significantly increased in hyperglycemic zebrafish.
- Aflibercept at 100 μg/mL was identified as a non-toxic and effective dose.
- Aflibercept treatment reduced retinal vessel diameter and inflammation in the zebrafish DR model.
- Molecular and histopathological efficacy of aflibercept was confirmed.
Conclusions:
- A functional zebrafish model for diabetic retinopathy has been successfully created.
- This model accurately reflects DR pathophysiology, including vascular changes and inflammation.
- The model is suitable for evaluating the efficacy of anti-diabetic retinopathy drugs like aflibercept.
- It can be utilized for high-throughput screening of novel therapeutic candidates for DR.
