The Role of Glutamate in Glaucoma and other related conditions

Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS). In the eye, glutamate is synthesized and released from retinal neurons and optic nerve cells. Glutamate receptors have been identified on both ganglion cell bodies and axons of the mammalian retina and optic nerve. Glutamate exerts its effects via ionotropic and metabotropic receptors, which are further classified into N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate, and metabotropic glutamate receptor subtypes.

In humans, glutamate is mainly involved in vision, learning, sleep, pain perception, mood, appetite, and memory. When glutamate levels fall in the brain, it may lead to neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. These neurological disorders affect the way the brain communicates and controls body movements. However, researchers have recently discovered that glutamate is not only associated with these neurological disorders, but it might also play a role in eye diseases like glaucoma and age-related macular degeneration.

In some forms of glaucoma, the production of glutamate increases in the retina. This results in increased stimulation of glutamate receptors leading to excessive influx of Ca2+ ions, which causes damage to retinal ganglion cells.

In the retina, glutamate is produced by retinal ganglion cells and transported to neighboring neurons. In the optic nerve, glutamate is released at synapses where it activates postsynaptic receptors. To maintain glutamate concentrations in the brain, glutamate transporters clear excess glutamate from the synaptic cleft. Studies show that glutamate transporter expression changes with age and some studies suggest that reduced glutamate transport may contribute to age-related visual impairment.

Researchers have shown that glutamate regulates intraocular pressure (IOP). IOP is the force exerted by fluid inside the eyeball on the front surface of the cornea causing bulging of the eyeball. Elevated IOP is related to many eye conditions such as open angle glaucoma, primary closed angle glaucoma and ocular hypertension. Therefore, reducing the amount of glutamate in the eyes could reduce IOP and prevent blindness. The study showed that reducing glutamate activity in mice caused significant lowering of IOP. Researchers believe that reducing glutamate activity would help lower IOP in people suffering from glaucoma.