An impairment of cellular interactions between the elements of the neurovascular unit contributes to the onset and/or progression of retinal diseases. The present study aims to examine how elements of the neurovascular unit are altered in a rat model of retinopathy of prematurity (ROP). Neonatal rats were treated subcutaneously with the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8 to induce ROP. Morphological assessments were performed of blood vessels, astrocytes and neuronal cells in the retina. Aggressive angiogenesis, tortuous arteries and enlarged veins were observed in the retinal vasculature of KRN633-treated (ROP) rats from P14 to P28, compared to age-matched control (vehicle-treated) animals. Morphological abnormalities in the retinal vasculature showed a tendency toward spontaneous recovery from P28 to P35 in ROP rats. Immunofluorescence staining for glial fibrillary acidic protein and Pax2 (astrocyte markers) revealed that morphological changes to and a reduction in the number of astrocytes occurred in ROP rats. The developmental cell death was slightly accelerated in ROP rats; however, no visible changes in the morphology of retinal layers were observed on P35. The abnormalities in astrocytes might contribute, at least in part, to the formation of abnormal retinal blood vessels and the pathogenesis of ROP.
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This study was supported by JSPS KAKENHI (Grant Number: 26460103, T.N.) and MEXT KAKENHI (Grant Number: 25122712, T.N.).
Conflict of interest
The authors declare that they have no conflicts of interest.
This study was approved by the Institutional Animal Care and Use Committee for Kitasato University (approval number: 17-19). The use of animals in this study was in accordance with institutional guidelines and in compliance with the Association for Research in Vision and Ophthalmology Statement.
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Nakano, A., Kondo, R., Kaneko, Y. et al. Changes in components of the neurovascular unit in the retina in a rat model of retinopathy of prematurity. Cell Tissue Res 379, 473–486 (2020). https://doi.org/10.1007/s00441-019-03112-9
- Endothelial cell
- Neuronal cell
- Vascular endothelial growth factor
- Vascular endothelial growth factor receptor tyrosine kinase inhibitor