Interference of the apoptotic signaling pathway in RGC stress response by SP600125 in moderate ocular hypertensive rats.

The aim of the present study was to investigate the effect of SP600125 (1,9-pyrazoloanthrone), an inhibitor of JNK, on apoptosis of retinal ganglion cells (RGCs) induced by moderate elevation of intraocular pressure (IOP) in male rats. IOP was elevated by suture-pulley compression on eyeballs. Cell apoptosis, expression of phosphorylated JNK (p-JNK) and cleaved caspase-3 in retina were studied by TUNEL staining and immunohistochemistry. The expression of c-Jun in retina was assayed by Western blot. Following IOP elevation (about 45 mmHg) for 6 h, the number of TUNEL, p-JNK and cleaved caspase-3 positive cells and the amount of c-Jun expression in retina were significantly increased. All these changes were reversed by SP600125 treatment. The immune positive cells for TUNEL, p-JNK and cleaved caspase-3 following IOP elevation were localized at the RGC layer. We conclude that moderate elevation of IOP for 6 h induced apoptosis of RGCs, and SP600125 treatment attenuated this process by suppressing c-Jun expression.