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

Apoptosis may contribute to retinal ganglion cell loss in glaucoma and glau coma models. Recent research has suggested that mitochondrially dependent a poptosis signaling may contribute to apoptosis in a rat model of glaucoma i nvolving chronic increases in intraocular pressure. In some for-ms of apopt osis, mitochondrially dependent signaling involves increases in mitochondri al membrane permeability and the mitochondrial release of factors that sign al 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 a nd facilitate megapore closure and reduce increases in mitochondria membran e permeability. Phosphorylated protein kinase B (Akt) serves as an integrat or for cellular survival signals and facilitates the megapore actions of BC L-2 and BCL-X-L, which could protect retinal ganglion cells against insults chat induce apoptosis. Several anti-apoptotic agents are being evaluated f or use in glaucoma, including brimonidine and propargylamines, which oppose mitochondrially dependent apoptosis through pathway involving phosphorylat ed Akt. (C) 2001 by Elsevier Science Inc. All rights reserved.