PURPOSE.To determine the modification of the glutamate-induced death of retinal neurons by endothelin (ET)-1. METHODS. Cultured retinal neurons from fetal rats were exposed to glutamate (1.0 mM) alone or glutamate with ET-1 (10 Ϫ10-10 Ϫ7 M) for 10 minutes. Neuronal death was assessed by the trypan blue exclusion or TUNEL assays at 2, 6, and 24 hours after the exposure. The effects of adding BQ-123 or BQ-788, ET A , and ET B receptor antagonists, respectively, in combination with ET-1 was also assessed. RESULTS. Immunohistochemical analyses showed that the ETs as well as ET A and ET B receptors were expressed on cultured retinal neurons consisting mainly of amacrine cells. A brief exposure of the cultured retinal neurons to glutamate alone significantly increased the number of dead cells, and the addition of ET-1 with glutamate caused a further significant increase in retinal neuronal death compared with the cells exposed to glutamate alone. A significant increase in neuronal death was detected at doses of 10 nM of ET-1 and higher after a 24-hour exposure (P Ͻ 0.05, Dunnett), whereas brief exposure of neurons to up to 1 M ET-1 alone did not cause delayed cell death of neurons. BQ-123 (10 nM) suppressed the enhancement of retinal toxicity caused by ET-1 (10 nM), whereas BQ-788 had no significant effect. CONCLUSIONS. These results indicate that ET-1 enhances glutamate-induced retinal cell death, possibly through ET A receptors. ET-1 may act synergistically with glutamate to damage retinal neurons under hypoxic conditions. (Invest Ophthalmol Vis Sci. 2005;46:4684 -4690)

To test the effect of activation of P2X 7 receptors on retinal blood velocity in diabetic rabbits. Methods: Immunohistochemical analysis was performed on healthy and diabetic rabbit eyes using P2X 7 receptor antibodies. Diabetes was induced using alloxan. Retinal blood velocity was measured with the laser speckle circulation analyzer. Visual function was assessed using electroretinography. Results: Cells in inner retinal layers were positive for anti-P2X 7 receptor antibodies in healthy rabbits. The distribution of positive cells extended to outer layers and some small vessels stained in diabetic rabbits. When assayed 24 hours after an intravitreal injection of 150 nmol of benzoylbenzoyl adenosine triphosphate (BzATP), a P2X 7 agonist, the retinal blood velocity in healthy rabbits was reduced by approximately 30%; this reduction

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