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Top-Nine of the Annual Basel Glaucoma Meeting
October 12-13, 2006, Basel, Switzerland
Maneli Mozaffarieh and Josef Flammer
The traditional glaucoma meeting at Basel creates a unique occasion to introduce and discuss various fundamental aspects of glaucoma. This year more than 300 participants from all over Europe, North America and Asia attended the meeting. The topics presented included basic pathophysiological mechanisms, and questions such as why IOP is increased or how IOP and vascular dysregulation lead to damage. Some of the interesting facts discussed are presented here.
- A more or less constant reduction in ocular blood flow can lead to atrophy in the optic nerve head, or in extreme cases, even to infarction. It is an unstable blood flow, however, that is linked to glaucomatous damage.
- The instability in blood flow leads to oxidative stress particularly in the mitochondria located numerously in the axons of the optic nerve head. This leads to production of the superoxide anion (O2.-) in the mitochondria.
- When astrocytes are activated, by mechanical or ischaemic stress, they produce nitric oxide (NO).
- The reaction between nitric oxide (NO) and superoxide anion (O2.-) produces the highly damaging peroxynitrite (ONOO-) which can diffuse along the axons towards the retina and the lateral geniculate inducing apoptosis.
- Oxidative stress leads to damage of a variety of macromolecules, such as lipids, proteins or DNA. DNA breaks can be observed both locally and systemically in circulating lymphocytes.
- Oxidative stress can lead to both a local and systemic upregulation of metalloproteinase 9 (MMP-9) which, in turn, digests the extracellular matrix inducing tissue remodelling and weakening the blood retinal barrier at the border of the optic nerve head.
- Endothelin-1 is particularly increased in patients that progress despite a normal IOP. Endothelin-1 and MMP-9 diffuse from the fenestrated vessels of the choroid to the surrounding of the ONH where they weaken the blood-brain barrier (BBB) of the local vessels. This can be demonstrated by fluorescence angiography. In extreme cases, the BBB is weakened to an extent that even erythrocytes can escape inducing the formation of commonly seen 'splinter haemorrhages'.
- Besides IOP lowering treatment, the elucidation of non-IOP lowering treatment (e.g., with ginkgo) for glaucomatous damage has become an area of increasingly active investigation.
- Non IOP lowering treatments include also nutritional sources of antioxidants: red wine, dark chocolate, green or black tea and coffee are all polyphenolic substances with free radical scavenging activity; coffee additionally contains the compound 3-methyl-1,2-cyclopentanedione (MCP) which has been shown to a selective scavenger of the peroxynitrite; bilberry is rich in anthocyanosides, which have strong scavenging properties, as a result of the positively charged oxygen atom in their structure.
