Abstract:

Distribution pattern of axonal cytoskeleton proteins in the human optic nerve head拒Glaucoma is one of the leading causes of blindness in developed world. It is progressive optic neuropathy where structural loss of retinal ganglion cell (RGC) axons corresponds with functional visual field defect. Glaucoma is distinguished from other optic neuropathies by its selective loss of RGC axons. Superior and inferior peripheral nerve sectors are found to be most vulnerable to pressure induced injury whereas inner temporal sector is most resilient. Pathogenesis behind the preferential axonal damage pattern is still poorly understood. Prof. Dao-Yi Yu (The University of Western Australia) showed that as RGC axons traverse a long distance through a number of different mechanical and extracellular environments along their projected path, it is expected that the cytoskeleton will play a critical role in maintaining axonal integrity. The distribution of cytoskeleton protein in the optic nerve head may therefore provide valuable information regarding the energetics and vulnerability of axonal injury in each compartment. Axonal cytoskeleton proteins are inherently linked to RGC health and disease. Intermediate filaments, microtubules, actin filament and microtubule associated proteins (MAPs) constitute axonal cytoskeletons. Cytoskeleton protein behaviour is shaped by physiological variables such as absolute tissue pressure and pressure gradients. Additionally, structural determinants of regional cytoskeleton protein concentration include myelin proteins and the pattern of mitochondrial distribution. The variation in mitochondrial organelle, myelin protein content and neural tissue pressure along the length of the human RGC axon could potentially influence the regional concentration of cytoskeleton protein subunits. This may help explain why the optic nerve head is injured in an asymmetrical fashion in many diseases including glaucoma.