Soluble forms of EphrinB2 and EphB4 reduce retinal neovascularization in a model of proliferative retinopathy.

Ephrin ligands and their Eph receptors are key regulators of endothelial cell (EC) proliferation, migration, adhesion, and repulsion during mammalian vascular development. The hypothesis was that these molecules also play a role in pathologic neovascularization (NV) in the mouse model of oxygen-induced retinopathy. C57BL/6 mice at postnatal day (P)7 were exposed to 75% oxygen (O(2)) for 5 days (until P12) and allowed to recover in room air to induce retinal NV. Retinas from unexposed and hyperoxia-exposed mice between P7 to P24 were analyzed specifically for EphrinB2 and EphB4 transcript expression by RT-PCR. Phospho-Eph (p-Eph) receptor was evaluated during active EC proliferation at P15 and P17 by immunohistology. Some hyperoxia-exposed mice had one eye injected intravitreally with 150 ng/1.5 microL of soluble EphrinB2/Fc or EphB4/Fc chimeras during transition from high O(2) to room air (P12) and injected again on P14. Contralateral eyes were injected with human IgG as the control. Preretinal nuclei and retinal blood vessels were quantified at peak disease (P17). EphrinB2 mRNA was constitutively expressed in the developing retina and was unchanged by hyperoxia. In contrast, EphB4 mRNA expression was modulated during normal retinal development and was altered by hyperoxia. Furthermore, p-Eph was detected in developing preretinal tufts, thus implying that Ephrin/Eph signaling system is active in this experimental model. Intravitreal injection of soluble versions of these molecules significantly reduced pathologic neovascularization. The number of preretinal nuclei in hyperoxia-treated mice was reduced by 66% (P < 0.05) in EphrinB2-injected eyes, whereas EphB4 treatment yielded a 69% reduction (P < 0.05), compared with control injections. Intraretinal vessel development was not altered by the injections. These results support the hypothesis that endogenous EphrinB2 and EphB4 are regulators of retinal NV during oxygen-induced retinopathy and may be useful targets for therapeutic intervention.

Zamora DO ，Davies MH ，Planck SR ，Rosenbaum JT ，Powers MR ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》

The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy.

Stitt AW ，McKenna D ，Simpson DA ，Gardiner TA ，Harriott P ，Archer DB ，Nelson J ... -  《-》

Altered retinal neovascularization in TNF receptor-deficient mice.

Ilg RC ，Davies MH ，Powers MR 《CURRENT EYE RESEARCH》

Increased expression of chemokine KC, an interleukin-8 homologue, in a model of oxygen-induced retinopathy.

Powers MR ，Davies MH ，Eubanks JP 《CURRENT EYE RESEARCH》

T2-TrpRS inhibits preretinal neovascularization and enhances physiological vascular regrowth in OIR as assessed by a new method of quantification.

Banin E ，Dorrell MI ，Aguilar E ，Ritter MR ，Aderman CM ，Smith AC ，Friedlander J ，Friedlander M ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》