Role of EphrinB2 Reverse Signaling in Pathological Retinal Neovascularization

Retinopathy of prematurity (ROP) is a potentially blinding retinal disease that affects prematurely born infants. ROP is characterized by abnormal blood vessel growth in the retina. In order to investigate a treatment for this condition, the mechanisms behind blood vessel growth involving ephrinB2 reverse signaling in pathological retinal neovascularization must be understood. Litters of transgenic ephrinB2lacZ/+ and WT mice were subjected to the murine model of ROP. 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 and analyzed to assess avascular tissue to total tissue ratio. Whole eyes harvested at P21 were sectioned, stained with hematoxylin and eosin, and 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. “When the mice are taken out of the hyperoxia condition and returned to normal oxygen level, a local tissue hypoxia will cause pathological growth of retinal superficial vessels stimulated through EphB4 and ephrinB2 signaling pathways. ”