Cellular Mechanisms of Angiogenesis in Neonatal Rat Models of Retinal Neurodegeneration

• Published in: International journal of molecular sciences 2019-09, Vol.20 (19), p.4759
• Main Authors: Asano, Daiki, Hokazono, Masaki, Hirano, Shogo, Morita, Akane, Nakahara, Tsutomu
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animal models; Animals; Animals, Newborn; Apoptosis; Aspartic acid; Astrocytes; Biomarkers; Blood vessels; Capillaries; Cyclin-dependent kinase inhibitor p21; Disease Models, Animal; endothelial cell; excitotoxicity; Eye (anatomy); Fluorescent Antibody Technique; Glial cells; Glutamate receptors; Growth factors; Homeostasis; Injuries; Kainic acid; Morphology; Mueller cells; N-Methyl-D-aspartic acid; Neonates; Neurodegeneration; Neuronal-glial interactions; Protein-tyrosine kinase receptors; Rats; Retina; retinal blood vessels; Retinal Degeneration - etiology; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; retinal glial cell; Retinal Neovascularization - etiology; Retinal Neovascularization - metabolism; Retinal Neovascularization - pathology; retinal neuronal cell; Retinal Neurons - metabolism; Retinal Neurons - pathology; Retinal Pigment Epithelium - metabolism; Retinal Pigment Epithelium - pathology; Retinal Vessels - metabolism; Retinal Vessels - pathology; Tyrosine; Vascular endothelial growth factor; Vascularization
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20194759

Νeuronal and glial cells play an important role in the development of vasculature in the retina. In this study, we investigated whether re-vascularization occurs in retinal neurodegenerative injury models. To induce retinal injury, -methyl-D-aspartic acid (NMDA, 200 nmol) or kainic acid (KA, 20 nmol) was injected into the vitreous chamber of the eye on postnatal day (P)7. Morphological changes in retinal neurons and vasculature were assessed on P14, P21, and P35. Prevention of vascular growth and regression of some capillaries were observed on P14 in retinas of NMDA- and KA-treated eyes. However, vascular growth and re-vascularization started on P21, and the retinal vascular network was established by P35 in retinas with neurodegenerative injuries. The re-vascularization was suppressed by a two-day treatment with KRN633, an inhibitor of VEGF receptor tyrosine kinase, on P21 and P22. Astrocytes and Müller cells expressed vascular endothelial growth factor (VEGF), and the distribution pattern of VEGF was almost the same between the control and the NMDA-induced retinal neurodegenerative injury model, except for the difference in the thickness of the inner retinal layer. During re-vascularization, angiogenic sprouts from pre-existing blood vessels were present along the network of fibronectins formed by astrocytes. These results suggest that glial cells contribute to angiogenesis in neonatal rat models of retinal neurodegeneration.