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Felicitas Bucher, Andreas Stahl, Gottfried Martin, Hansjürgen Agostini; Retinal Astrocytes in the Mouse Model of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5587.
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Retinal neovascularization has been intensively investigated in the mouse model of oxygen-induced retinopathy (OIR). The role of astrocytes for vascular loss and reactive angiogenesis, however, is not fully understood. Due to their stellar morphology, only semi-quantitative analysis has yet been possible. This study presents data on the kinetics of retinal astrocytes in relation to changes in the vascular bed during the OIR model based on a quantitative approach.
In the OIR model, mice are exposed to 75% oxygen from post-natal day 7 (P7) to P12 (hyperoxic phase). After return to room air, the avascular area of the retina becomes hypoxic and responds with physiologic and pathologic revascularization from P12 to P21. In this study, reporter mice expressing histone-bound GFP under the control of the Pdgfra promoter were used to identify astrocyte nuclei in the murine retina. The astrocytic density across the retina was determined at different times during the OIR model using the automated ImageJ macro AuTOCellQuant.
The inner surface of the murine retina is densely populated with astrocytes at P7. From P8 to P10 during the hyperoxic phase of the OIR model, astrocytic density strongly decreases in the avascular zone due to apoptotic cell death compared to controls not exposed to 75% oxygen. The low astrocytic cell density persists throughout the hypoxic phase. An increase in cellular density to a normal level of 800 cells/mm2 can only be observed in revascularized parts of the avascular zone.
Reporter mice expressing nuclear GFP in retinal astrocytes can be used to examine the kinetics of astrocytes during physiological angiogenesis and the OIR model on a quantitative level. Our study found a strong decrease of astrocytic cell density in the avascular zone during the hyperoxic phase, as opposed to earlier studies describing loss of astrocytic Gfap expression only during the hypoxic phase. These results indicate that astrocyte damage might occur early in proliferative retinopathy, even before the onset of retinal hypoxia. In turn, in the OIR model, interventional treatment to protect retinal astrocytes has to take place before the hyperoxic phase.
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