PUBLICATION
High glucose-induced changes in hyaloid-retinal vessels during early ocular development of zebrafish: A short-term animal model of diabetic retinopathy
- Authors
- Jung, S.H., Kim, Y.S., Lee, Y.R., Kim, J.S.
- ID
- ZDB-PUB-150816-1
- Date
- 2016
- Source
- British journal of pharmacology 173(1): 15-26 (Journal)
- Registered Authors
- Jung, Seung-Hyun
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Diabetic Retinopathy/chemically induced
- Diabetic Retinopathy/metabolism*
- Disease Models, Animal*
- Glucose/adverse effects*
- Larva/drug effects
- Larva/metabolism
- NG-Nitroarginine Methyl Ester/pharmacology
- Nitric Oxide/biosynthesis
- Ranibizumab/pharmacology
- Receptors, Vascular Endothelial Growth Factor/metabolism
- Retinal Vessels/drug effects*
- Retinal Vessels/metabolism
- Retinal Vessels/pathology
- Tight Junction Proteins/metabolism
- Vascular Endothelial Growth Factor A/biosynthesis
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/biosynthesis
- PubMed
- 26276677 Full text @ Br. J. Pharmacol.
Citation
Jung, S.H., Kim, Y.S., Lee, Y.R., Kim, J.S. (2016) High glucose-induced changes in hyaloid-retinal vessels during early ocular development of zebrafish: A short-term animal model of diabetic retinopathy. British journal of pharmacology. 173(1):15-26.
Abstract
Background and purpose Although a variety of animal models have been used to test drug candidates and examine diabetic retinopathy (DR) pathogenesis, timesaving and inexpensive models are still needed to evaluate the increasing number of therapeutic approaches.
Experimental approach We introduce a model for DR using the early stage of transgenic zebrafish (flk:EGFP) by treating embryos with 130 mM glucose for 3 days. Lenses from zebrafish larvae were isolated and developed using 3% trypsin, and changes in hyaloid-retinal vessels were analysed using fluorescent stereomicroscopy. In addition, expression of tight-junction proteins (such as ZO-1), non-osmotic effects, phenocopy by hypoxia condition, Vegf expression by RT-PCR, and nitric oxide (NO) production by 4,5-diamino-fluorescein diacetate (DAF-FA-DA) were tested in high glucose (HG)-induced zebrafish larvae at 6 days post-fertilization (dpf). We also examined the pharmacological effects of the VEGFR and NO inhibitors and VEGF antibody drug (ranibizumab).
Key results We established a short-term animal model for the study of diabetic retinal vascular dysfunction and drug screening. In this model, dilation of hyaloid-retinal vessels caused morphological lesions with disruption of tight-junction proteins, overproduction of Vegf mRNA, and increased NO production. We also show that the VEGFR and NO inhibitors and ranibizumab reduced HG-induced dilation of hyaloid-retinal vessels.
Conclusions and implications These findings suggest that glucose-treated zebrafish larvae may be used for screening and drug discovery for DR, particularly for tight-junction-, VEGF-, and NO-related pathologies observed in retinal vessel disorders. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping