Apoptosis is the genetically regulated form of cell death that permits the safe disposal of cells at the point in time when they have fulfilled their intended biological function.
Examples of apoptosis can be cited throughout the whole of the animal and plant kingdoms.
It is a vitally important process during normal development and the adult life of many living organisms. In humans, dysregulation of apoptosis can result in inflammatory, malignant, autoimmune, and neurodegenerative diseases.
In addition, infectious agents, including viruses, exploit cellular apoptosis in the host to evade the immune system. This review gives a brief historical perspective of some of the landmark discoveries in apoptosis research.
The morphological and biochemical stages of apoptosis are then covered, followed by an overview of how it can be studied in the laboratory. Finally, the implications for therapeutic intervention in disease treatment are discussed.
Apoptosis and anti-apoptosis signalling in glaucomatous retinopathy.
OBJECTIVERecent 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.
METHODSRecent 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.
CONCLUSIONSBrimonidine 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.