Central/branch retinal artery/vein occlusion, diabetes, glaucoma and, possibly, age related macular degeneration (AMD) are conditions associated with retinal ischaemia. All these diseases may lead to severe sequelae. Therefore, the management of retinal ischaemia is crucial.
After ischaemia/reperfusion (I/R), large amounts of reactive oxygen species (ROS) such as H2O2 are produced. These ROS attack nearby cells and cause tissue damage. Moreover, excessive release of excitatory transmitters such as the glutamate from ischaemia affected neurons leads to neuronal overstimulation and unwanted depolarisation. Consequently, neurons that possess a high density of glutamate receptors are most at risk. This explains why neurons such as retinal ganglion cells (RGCs) and amacrine cells, as well as their neuronal processes, which are located in the inner retina, are vulnerable to (I/R).
Ischaemia induces angiogenesis. Furthermore, in the retina, angiogenesis is often disorganized and typically results in oedema and haemorrhage; these have adverse effects on visual function. There is an urgent need for therapies that promote endogenous protective responses and prevent harmful angiogenesis. Increased levels of hypoxia-inducible factor-1Alpha (HIF-1 Alpha) have been found to be present after retinal ischaemia. HIF-1 binds to the hypoxia response element in hypoxia-responsive target genes, and triggers the expression of vascular endothelium growth factor (VEGF) and matrix metalloproteinases (MMPs). Liu et al. have shown that oxidative stress in human retinal pigment epitheliums (hRPEs) results in up-regulation of VEGF and MMP-9. Additionally, ischaemia has been proved to result in irreversible RGC loss that is accompanied by MMP-9 up-regulation. All the above evidence suggests that the over-expression of HIF-1 Alpha, VEGF and/or MMP-9 in the retina or in RGCs is directly related to ischaemic/ischaemic-like insult, but the relationship in more detail is unknown.
S-allyl L-cysteine (SAC), an active organosulfur compound in aged garlic extract, has been reported to possess antioxidative activity. In macrophages and endotheliums, SAC has been shown to exhibit potent antioxidative effects involving the scavenging of superoxide radicals, hydroxyl radicals and hydrogen peroxide.