Apoptosis and anti-apoptosis signalling in glaucomatous retinopathy.
OBJECTIVE
Recent studies in the post-mortem human retina have suggested that apoptosis contributes to retinal ganglion cell (RGC) loss in glaucoma. If apoptosis contributes significantly to glaucomatous RGC loss, and if the specific apoptosis signalling pathways for glaucomatous apoptosis can be determined, agents that interrupt or oppose the signalling have the potential to slow the progression of glaucoma.


METHODS
Recent data in animal models indicate that mitochondrially-dependent apoptosis contributes to RGC loss in glaucoma. Mitochondrially-dependent apoptosis involves proteins like BAX that increase mitochondrial membrane permeability and promote apoptosis and proteins like BCL-2 that decrease mitochondrial membrane permeability and reduce apoptosis. New protein synthesis induced by the alpha-2 agonist, brimonidine, prevents decreases in the levels of BCL-2 and thereby reduces mitochondrially-dependent apoptosis.


CONCLUSIONS
Brimonidine appears to maintain BCL-2 levels by supporting the activity of an intrinsic anti-apoptosis signalling system that involves phosphorylation of protein kinase B. Phosphorylated protein kinase B appears to counteract the apoptosis signalling mechanisms which operate in glaucomatous retina.
Tatton
W G
WG
Department of Ophthalmology, Mount Sinai Medical Center, New York, New York 10029, USA. william.tatton@mssm.edu
Chalmers-Redman
R M
RM
Tatton
N A
NA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068438:Brimonidine Tartrate; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D015398:Signal Transduction
D000316:Adrenergic alpha-Agonists; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt