What is the present pathogenetic concept of glaucomatous optic neuropathy?

Abstract

Glaucomatous optic neuropathy implies loss of neural tissue, activation of glial cells, tissue remodeling, and change of blood flow. The blood flow reduction is not only secondary but has a primary component. Activation of astrocytes leads to an altered microenvironment. An unstable ocular perfusion, either due to IOP fluctuation or a disturbed autoregulation (due to primary vascular dysregulation syndrome) leads to a mild reperfusion injury. The superoxide (O(2)(-)) anion produced in the mitochondria of the axons, fuses with the nitric oxide (NO) diffusing from the astrocytes, leading to the damaging peroxynitrite (ONOO(-)). It is possible that the diffusion of endothelin and metalloproteinases to the surrounding of the optic nerve head leads to a local vasoconstriction and thereby increases the risk for venous occlusion and weakens the blood-brain barrier, which in extreme situations results in splinter hemorrhages. Activated retinal astrocytes can be visualized clinically. The involvement of primary vascular dysregulation in the pathogenesis of glaucomatous optic neuropathy may explain why women, as well as Japanese, suffer more often from normal-tension glaucoma.