Ganglion cell death in glaucoma: pathology recapitulates ontogeny

I review some improvements in our knowledge about the death of retinal ganglion cells in glaucoma during the last 20 years. These include the realisation that glaucoma damage precedes its detection by perimetry, the fact that the lamina cribrosa is a major site of axonal injury to ganglion cells, and the association between regional structure of optic nerve head connective tissue and the pattern of glaucoma damage. The selective susceptibility of larger retinal ganglion cells and its functional significance are described. Apoptosis is the mode of cell death in at least some ganglion cells in experimental glaucoma. This supports a theory that retrograde axonal transport failure leads to loss of trophic factor influence on ganglion cells, causing them to initiate their own suicide. As a consequence of this theory, two therapeutic avenues are suggested for prevention of glaucoma injury and cell death: delivery of trophic factors and manipulation of ganglion cell genetic expression of controlling influences over programmed cell death.