Role of ephrinB2 and EphB4 in mouse retinal angiogenesis

Eph receptors are transmembrane RTKs that are activated by clustering that occurs on binding to membrane-tethered ephrin ligands. Two members or the ephrin family, ligand ephrinB2 and receptor EphB4 are known for their ability to distinguish arterial versus venous endothelium upon their expression on the cell surface. Both substances are playing an important role for the formation of the primary vascular network during embryonal development, as well as for the distinction and boundary formation between arteries and veins. <br>In order to verify the presence of both substances in the retina RNA was isolated from retinal tissue of new-born mice. A reverse transcription into cDNA, was performed using the polymerase chain reaction (RT-PCR). cDNA was amplified in a PCR cycler using ephrinB2 and EphB4 specific primers. <br>To investigate the effect on pathological retinal blood vessel formation, dimeric ephrinB2 or EphB4 was injected in the vitreous of mice using the murine model of oxygen induced retinopathy (OIR). Retinal whole mounts were prepared after fluorescein-dextran perfusion and neovascularization features were quantified in a blinded fashion. The criteria taken into account were blood vessel tuft formation, extraretinal neovascularization, non-perfusion areas, tortuosity of the vessels and neovascularization of the optic disc. <br>In order to visualise the effect of the substances on physiological retinal blood vessel development, the substances were injected intravitreally in P6 or P7 mice and after seven days in room air, retinal whole mounts were prepared and evaluated. <br>Concerning pathological angiogenesis, a single intravitreal injection of dimeric ephrinB2 or EphB4 increased the retinal angioproliferative changes significantly compared to the control eyes. No evident effects on physiological angiogenesis were observed. The PCR amplification experiments showed that ephrinB2 and EphB4 are detectable in the retinal tissue of mice at different stages of postnatal development. <br> <br>These findings provide evidence that ephrinB2 ligand and EphB4 receptor are involved in pathologic retinal angiogenesis. It is possible to modify the angiogenesis response by manipulating their signalling in the retina. Blocking their action might open new possibilities in the treatment of angioproliferative retinopathy.

Author dc:creator

• Gogaki, Eleni

Contributors dc:contributor

• Hansen, Lutz-Lothar

• retina
• angiogenesis
• ephrins

Repository record source_url

https://freidok.uni-freiburg.de/data/1071

OAI identifier oai:identifier

oai:freidok.uni-freiburg.de:1071