It was not so long ago that glaucomatologists and neuro-ophthalmologists lived in different worlds. As our understanding of glaucoma has migrated to appreciate it as, first and foremost, an optic neuropathy, these disparate worlds – and associated treatment interventions – have begun to merge.

Nowhere is this more compelling than in the world of neuroprotection. For decades clinicians caring for those with glaucoma have directed their intervention at lowering the major risk factor of the disease’s progression – pressure.

Understandably, this was recognised as treating not the disease, but a proxy of the disease. Yet this tradition and approach has been so widespread that we lost sight of our ultimate goal, saving the integrity of the retinal ganglion cells and their axons. As our thinking has evolved, we recognised that it is damage to the axons of the retinal nerve fibre that is the final common pathway for glaucomatous damage; from this insight emerged the idea of protecting those axons with an additional methodology to simply lowering intraocular pressure.

What is neuroprotection? It is the strategy of targeting those very retinal ganglion cells and their axons – card carrying members of the central nervous system – to shield these cells from insult, injury, or degeneration.

The objective of neuroprotection is to limit physiologic dysfunction and death of these cells of the central nervous system, slow their progressive damage in disease and attempt to maintain the integrity of anatomy and physiology of cells and their interactions in the eye.

This initiative – still in its infancy and not yet bearing fruit – makes use of multiple possible interventions. Strategies examined in the past have included those which inhibit apoptosis, decrease oxidative stress, alter mitochondrial dysfunction, boost free radical scavengers, alter excitatory modulators, promote active neurotrophic factors, modulate ion channel actions, and chelation of metal ions. Thoughts of active gene therapies and stem cell interventions are newer, still.

Both oxidative stress and excitotoxicity are thought to initiate neuron cell death, and when conjoined, seem to have synergistic effects that cause even more degradation than either on their own. Restricting excitotoxicity and oxidative stress are an important aspect of neuroprotection and this should be equally true in glaucoma as in any other optic neuropathy. Much of the efforts of neuroprotection have included glutamate antagonists and antioxidants, each of which strives to limit excitotoxicity and oxidative stress respectively.

The good news is that researchers are thinking about this avenue. The bad news is that they have not yet hit upon a successful and commercially viable product. The import of these initiatives is much wider than just ophthalmology and optic neuropathies, for any intervention that successfully retards neuronal cell loss will have immediate and obvious relevance to other neurologic diseases, be they acute or chronic.

When we can actively protect those retinal ganglion cells in glaucoma, we may be able to generalise that protection and apply it to more classic neurologic disorders such as Alzheimer's disease, spinal cord trauma, stroke, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and conceivably even the effects of aging.

The eye is arguably the best tissue to explore such neuroprotection in, and glaucoma perhaps the best disease model for induced effects of cellular protection and anatomic integrity. Both the tissue’s anatomic integrity and physiologic function can be directly seen and measured with optical coherence tomography and formal perimetry, and our success of protecting retinal ganglion cells awaits the success of neuroprotection-ists.

Stay tuned!


Prof Barrett Katz is the head
of the neuro-ophthalmology
and glaucoma sections at
ISOPT Clinical


Barrett Katz:

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