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Laura Ah-Kye, Tejas Kumar, Senthil Selvam, Parisa Naser, Almas Dawood, Paul McMenamin, Marcus Fruttiger; Characterisation of retinal vascular growth and retinal astrocytes in a novel oxygen-induced retinopathy murine model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3455.
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© ARVO (1962-2015); The Authors (2016-present)
A novel murine model of oxygen-induced retinopathy (OIR) exposes mice to 75% oxygen (O2) from post-natal day (P) 0 to P7 (McMenamin et al, IOVS, in press). The pathological features generated in this model have been reported to be reflective of persistent and severe retinopathy of prematurity (ROP). We sought to explore the underlying developmental and cellular mechanisms that lead to the distinct phenotype of this model.
Retinal whole-mounts and cross-sections of enucleated OIR model eyes were visualised at P3, P7, P14 and P21, using immunohistochemistry labelling of endothelial cells (via isolectin-IB4) and retinal astrocytes (via glial fibrillary acidic protein, GFAP).
At the early hyperoxic stages (P3 and P7), there was absent vascularisation with increased density of retinal astrocytes in comparison to controls. At P14 and P21 there was significant hyaloid hypertrophy and retinal-hyaloid anastomoses, which appeared to source abnormal vessels at the peripheral retina. Quantitative analysis revealed significantly decreased GFAP expression and lack of astrocyte differentiation at the early P7 time-point, in comparison to controls (P<0.05). In contrast, at P21, we noted increased GFAP expression in comparison to controls (P<0.05). Retinal astrocytes were located on the innermost part of the retina as elongated cells, with no relation to the overlying vasculature.
In this OIR model, normal retinal vascularisation is almost entirely prevented during the early stages by O2 exposure. Penetration of hyaloid vessels at distinct locations in the retina lead to the delayed pattern of abnormal vascular growth, which is not associated with an astrocyte template. The abnormal hyaloid growth is induced by the hypoxic retina on return to normal air. Interruption of normal retinal astrocyte and endothelial cell interaction may occur due to the lack of astrocyte differentiation during the hyperoxia phase. Finally, contact with hyperplastic vasculature leads to upregulation of GFAP expression. These observations can be used as a basis for further enquiry into pathogenic mechanisms in this model which may convey processes occurring in severe ROP infants.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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