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K. E. Mason, A. C. Taylor, P. A. Yates, S. M. Peirce; Role of EphrinB2 Reverse Signaling in Pathological Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3335.
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© ARVO (1962-2015); The Authors (2016-present)
The receptor tyrosine kinase EphB4 and its ligand ephrinB2 are known to be important players in postnatal angiogenesis and microvascular remodeling. However, the specific roles of EphB4 and ephrinB2 signaling in retinal hypoxia-induced neovascularization remain unclear. The objective of this study was to investigate the specific role of ephrinB2 reverse signaling in pathological retinal neovascularization using the standard murine model of retinopathy of prematurity (ROP).
Litters of transgenic ephrinB2lacZ/+ and WT mice were subjected to the murine model of ROP. (Transgenic ephrinB2lacZ/+ mice possess defective ephrinB2 reverse signaling but undisrupted forward signaling through EphB4.) EphrinB2lacZ/+ and WT mice were housed in 75% O2 from P7 until P12. The neovascularization response was quantified through the analysis of the avascular tissue/total tissue ratio and the formation of preretinal neovascular tufts. Retinas harvested at P17 were whole-mounted and stained with lectin to visualize the vasculature. Confocal microscopy was used to obtain images of superficial retinal networks. The images were then analyzed to assess avascular tissue to total tissue ratio. Whole eyes harvested at P21 were sectioned and stained with hematoxylin and eosin. Using 20x images of whole-eye sections, the number of preretinal nuclei per section was measured.
The avascular tissue/total tissue ratio was significantly increased in the ephrinB2lacZ/+ mice compared to the WT mice (0.26 ± 0.0063 vs. 0.14 ± 0.017, p < 0.005). Also, the number of preretinal vascular tufts per section was significantly decreased in ephrinB2lacZ/+ mice as compared to WT controls (22.9 ± 2.2 vs. 39.1 ± 3.7, p ≤ 0.001).
The results from this study indicate that mice with decreased ephrinB2 reverse signaling exhibit an attenuated neovascularization response in the murine model of ROP. Thus, our results provide evidence for a pro-angiogenic role of ephrinB2 reverse signaling in postnatal pathological retinal neovascularization.
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