Intrinsic survival mechanisms for retinal ganglion cells.
Retinal ganglion cells (RGCs) undergo programmed cell death (apoptosis) after axonal injury. This cell death is mediated by several mechanisms, including deprivation of neurotrophic factors, alterations in gene expression, and production of reactive oxygen species. However, death of RGCs is delayed after axonal injury, and a significant number survive even after several days. This suggests that RGC death is not an immediate result of axonal injury, and that other pro-survival factors may play a role. While we and other researchers have focused on the mechanisms of cell death after axonal injury, it may be that determining the regulation of cell survival mechanisms may lead to innovative methods for neuroprotection. The final common pathway of glaucomatous optic neuropathy is RGC death, probably via damage to their axons occurring at or near the lamina cribrosa. Axonal injury leads directly (1) or indirectly (2) to the death of retinal ganglion cells. We and others have demonstrated that axotomy is associated with RGC apoptosis (3-7) as well as specific changes in expression of certain genes at the mRNA and protein level (8, 9). Reactive oxygen species may also be part of the pathway for RGC death (10, 11). We therefore hypothesize that axotomy leads to molecular events that are potentially destructive to RGCs, but also induces changes that are potentially protective against cellular injury. If this is the case, then RGC death from axonal injury would result not only from initiation of apoptosis, but also from failure of intrinsic neuroprotective mechanisms. It should therefore be theoretically possible to modulate these two classes of responses, and thus improve RGC cell survival after axotomy.
Levin
L A
LA
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, USA. llevin@macc.wisc.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001369:Axons / Q000502:physiology; D019771:Axotomy; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D009900:Optic Nerve / Q000502:physiology; D017382:Reactive Oxygen Species / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology*
D017382:Reactive Oxygen Species