Ephrin-A5 Is Involved in Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy
| Autor: | Wei Du, Lvzhen Huang, Xin Tang, Xiaoxin Li, Jiarui Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Article Subject MAP Kinase Signaling System Angiogenesis Retinal Neovascularization Biology General Biochemistry Genetics and Molecular Biology Small hairpin RNA Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Retinopathy of Prematurity RNA Messenger RNA Small Interfering Protein kinase B Retina Gene knockdown General Immunology and Microbiology Retinal General Medicine medicine.disease Ephrin-A5 eye diseases Up-Regulation Cell biology Mice Inbred C57BL Oxygen Disease Models Animal 030104 developmental biology medicine.anatomical_structure Animals Newborn chemistry Gene Knockdown Techniques Intravitreal Injections 030221 ophthalmology & optometry Medicine Ephrin A5 sense organs Research Article Retinopathy |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2020 (2020) |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2020/7161027 |
| Popis: | Retinal neovascularization (RNV) is an important pathological feature of vitreoretinopathy that can lead to severe vision loss. The purpose of this study was to identify the role of ephrin-A5 (Efna5) in RNV and to explore its mechanism. The expression pattern and biological significance of Efna5 were investigated in a mouse model of oxygen-induced retinopathy (OIR). The expression of Efna5 and downstream signaling pathway members was determined by RT-PCR, immunofluorescence, immunohistochemistry, and western blot analyses. shRNA was used to knockdown Efna5 in the retina of the OIR mouse model. Retinal flat mounts were performed to evaluate the impact of Efna5 silencing on the RNV process. We found that the Efna5 was greatly upregulated in the retina of OIR mice. Elevated Efna5 mainly colocalized with the retinal vessels and endothelial cells. We then showed that knockdown of Efna5 in OIR mouse retinas using lentivirus-mediated shRNA markedly decreased the expression of Efna5 and reduced the retinal neovascularization and avascular retina area. We further showed hypoxia stimulation dramatically increased both total and phosphorylation levels of ERK1/2 and the phosphorylation levels of Akt in OIR mice. More importantly, knockdown of Efna5 could inhibit the p-Akt and p-ERK signaling pathways. Our results suggested that Efna5 may regulate the RNV. This study suggests that Efna5 was significantly upregulated in the retina of OIR mice and closely involved in the pathological retinal angiogenesis. |
| Databáze: | OpenAIRE |
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