Calcium channels are involved in EphB/ephrinB reverse signaling-induced apoptosis in a rat chronic ocular hypertension model

Erythropoietin-producing hepatocyte receptor B (EphB)/ephrinB reverse signaling has been revealed to be activated in chronic ocular hypertension (COH) by increasing the apoptosis of retinal ganglion cells (RGCs). However, the exact mechanism is not well understood. The present study investigated the involvement of Ca(2+) channels in the apoptosis of RGCs induced by EphB/ephrinB reverse signaling in a rat CHO model, which was established by cauterizing 3 out of the 4 episcleral veins. The expression levels of four voltage-gated Ca(2+) channel subunits (Ca(v)3.1–3.3 and Ca(v)1.2) were detected using immunofluorescence and western blot analysis. TUNEL staining was performed to assess RGC apoptosis following an injection with the T type Ca(2+) channel blocker. Ca(2+) channels, mainly the T type, were upregulated in COH rat retinas when compared with the sham group (P<0.01). Additionally, the Ca(v)3.2 subunit of T type calcium channels was predominantly expressed in Müller cells and RGCs, such as ephrinB2. Furthermore, an intravitreal injection of the Ca(2+) channel blocker Mibefradil (3 µM) reduced EphB2-fragment crystallizable region-induced RGC apoptosis in normal rats. Thus, the results suggest that Ca(2+) channels in a COH model may be a pathway involved in ephrinB/EphB signaling-induced RGC apoptosis.