Abstract
Purpose: :
To examine the retinal glial reaction in the murine oxygen-induced retinopathy model.
Methods: :
Neonatal C57BL/6j mouse pups (P7) were maintained for 5 days in 75 ± 3% oxygen, and then returned to room air (relative hypoxia) at P12. Eyes were enucleated between P18 and P26, and frozen sections were prepared. Sections were examined using immunohistochemistry with antibodies against glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA), a cell proliferation marker. Labeled isolectin-B4, was used as an endothelial marker.
Results: :
Isolectin-B4-positive neovascular tufts were present on the retinal surface where they extended into the vitreous cavity. Several neovessels were also present external to the ganglion cell layer as well, from P18 to P21. Linear expression of GFAP gradually increased within Muller glial processes during P18 and P21, however the processes did not surround the neovessels. GFAP-positive glial processes divided and surrounded neovessels between P21 and P23; several of these neovessels were occluded by eosinophilic material. PCNA-positive endothelial cells were identified in the stalk, but not at the tip of neovessels growing into the vitreous. In contrast, PCNA immunoreactivity was not detected in glial cells. At P26, there were no neovessels growing into the vitreous cavity, and neovascular endothelial cells were surrounded by GFAP-positive glial processes.
Conclusions: :
Prominent non-proliferative reactive gliosis takes place on the retina during vessel regression phase in hypoxia-induced angiogenesis. Retinal glial cells play an important role in regression of neovessels, which might represent a novel therapeutic target for retinal neovascularization.
Keywords: retinal glia • pathology: experimental • neovascularization