Maintaining mitochondrial membrane impermeability: An opportunity for new therapy in glaucoma?

Apoptosis may contribute to retinal ganglion cell loss in glaucoma and glaucoma models. Recent research has suggested that mitochondrially dependent apoptosis signaling may contribute to apoptosis in a rat model of glaucoma involving chronic increases in intraocular pressure. In some for-ms of apoptosis, mitochondrially dependent signaling involves increases in mitochondrial membrane permeability and the mitochondrial release of factors that signal for cell degradation. Opening of a multi-protein, mitochondrial megapore is one factor Brat contributes to the increased permeability and some anti-apoptotic proteins, particularly BCL-5 and BCL-X-L, bind at the megapore and facilitate megapore closure and reduce increases in mitochondria membrane permeability. Phosphorylated protein kinase B (Akt) serves as an integrator for cellular survival signals and facilitates the megapore actions of BCL-2 and BCL-X-L, which could protect retinal ganglion cells against insults chat induce apoptosis. Several anti-apoptotic agents are being evaluated for use in glaucoma, including brimonidine and propargylamines, which oppose mitochondrially dependent apoptosis through pathway involving phosphorylated Akt. (C) 2001 by Elsevier Science Inc. All rights reserved.