Memantine blocks mitochondrial OPA1 and cytochrome c release and subsequent apoptotic cell death in glaucomatous retina.

摘要: Purpose—To determine whether intraocular pressure (IOP) elevation alters OPA1 expression and triggers release, as well the uncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist memantine blocks release subsequent apoptotic cell death in glaucomatous DBA/2J mouse retina. Methods—Preglaucomatous mice received (5 mg/kg, i.p. injection, twice a day for 3 months) IOP eyes was measured monthly. RGC loss counted following Fluoro-Gold labeling. OPA1, Dnm1, Bcl-2 Bax mRNA were by Taqman qPCR. protein assessed immunohistochemistry Western blot. Apoptotic TUNEL staining. Results—Memantine treatment significantly increased survival mice. Memantine 75 kDa isoform but did not alter 80 90 isoforms. The isoforms of cytosol vehicle-treated retinas decreased memantine-treated retinas. immunoreactivity photoreceptors both vehicle- outer plexiform layer only blocked GCL, gene expression, expression. Conclusions—OPA1 from mitochondria retina is inhibited blockade activation. Because this effect accompanied apoptosis blockade, activation may involve distinct mitochondria-mediated pathway.