Neuroprotection : The Future of Glaucoma Therapy

Boonsong Wanicvhwechaungruang, M.D.

ABSTRACT : Glaucoma is a neurodegenerative disease, which intraocular pressure (IOP) is a major risk factor. However, the “non-IOP” factors such as genetics, microcirculation, neurotrophic factors also play roles in pathophysiology of the disease. Opitc nerve head ischemia in one of the initial events of the cascade, followed by intracellular energy depletion of the presynaptic neurons. The neurons abnormally release glutamate to the retinal ganglion cells. Glutamate will synapse to N-methyl-D-aspartate (NMDA) receptor, induced Ca²+ influx into the retinal ganglion cells. Nitric oxide syntrase (NOS) activation and nitric oxide (NO) formation, free radical oxygen species, mitochondria dysfunction, lipid peroxidation, and neurotrophin deprivation, lead the cells to die (apoptosis). The environment changed after death (increased extracellular glutamate), leads the neighboring cells to secondary degeneration. The degeneration is a possible cause of progressive visual loss in a so-called “controlled IOP” of glaucoma. Neuroprotection is the strategy to protect the neurons or retinal ganglion cells that take risk to die from any underlying diseases. Increasing blood flow to the optic nerve head, glutamate antagonists, inhibition of nitric oxide syntrase, up-regulation of antiapoptotic genes, supplement of free radical scavengers, up-regulation of neurotrophin, may be the modalities of additional treatments for glaucoma. In experimental glaucoma, neuroprotection appears to be effective in protection of ganglion cells loos. Yet, in human glaucoma, we lack of evidences of neuroprotection on its therapy. Hopefully, neuroprotection will be available in the future for treatment of this dreadful disease.

Thai J Ophthalmol 2000 : January-June 14(1) : 65-83.