HB-EGF: increase in the ischemic rat retina and inhibition of osmotic glial cell swelling

We determined whether the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the sensory rat retina alters during ischemia-reperfusion, and whether HB-EGF affects the osmotic swelling which is a characteristic feature of Müller glial cells after ischemia. Transient retinal ischemia was induced by elevation of the intraocular pressure for 1 h. Western blots revealed an upregulation of HB-EGF in the retina at 1, 3, and 7 days after reperfusion. HB-EGF inhibited the swelling of glial cells in retinal slices, via stimulation of the synaptic release of glutamate and subsequent activation of glial metabotropic glutamate receptors which resulted in an autocrine release of purinergic receptor agonists. Finally, activation of A1 receptors resulted in opening of glial K(+) and Cl(-) channels. It is suggested that the increased expression of HB-EGF and the inhibition of glial cell swelling may be parts of a protective role of HB-EGF in the ischemic retina.