• Written By: Darrell WuDunn, MD, PhD
    Comprehensive Ophthalmology, Glaucoma

    This article suggests an entirely new way of thinking about the pathogenesis of glaucomatous optic neuropathy. It posits that glaucoma is a disease of the central nervous system that starts in the brain and works its way back to the retina.

    To test their hypothesis, researchers injected a rodent model of glaucoma with cholera toxin β-subunit (CTB) to track the course of retinal ganglion cell neurons (RGC) through layer III of the superior colliculus. They found that the loss of RGCs in the superior colliculus, as measured by a lack of CTB, did not correlate with IOP, and that failure of RGC transport occurs in the SC first and then at more interior sites in order of increasing proximity to the eye, until arriving at the retina where transport eventually fails.

    The experiment shows that even though the pressure-induced insult occurs at the lamina cribrosa, optic nerve dysfunction begins to occur distally in the midbrain. An analogy to this would be an injury to the elbow causing tingling in the fingers.

    Moreover, the study indicates that the retinal ganglion cell dysfunction in transport occurs before physical degeneration of the cell axon. This implies that retinal nerve fiber function could be restored before permanent degeneration occurs. It is unclear if the same phenomenon occurs in human glaucoma and a similar effect in humans would be very difficult to test. However, if the same effect occurs in humans, then it might someday be possible to detect glaucomatous damage to the optic nerve - perhaps by some type of imaging technology such as a future generation functional MRI - before physiologic abnormalities occur in the retina nerve fiber layer.

    While much further research in this area is required before it would have any clinical usefulness, the present study opens new avenues to explore to help improve glaucoma diagnosis and management.