Eye-Opening Insights into Neural Degeneration in Glaucoma

Triple Helix
4 hours ago
5 min read

Written by: Nhi Nguyen ‘28

Edited by: Rocky Mattos-Canedo ‘26

Consider this: of your five senses, which one would you least want to lose?

While sensory loss of any variety can adversely impact daily life, most individuals report that losing their sense of sight would be the most devastating (2). The eyes, being the gateway to the visual system, connect human perception to the surrounding optical environment. However, this system is quite delicate—over 24 million Americans are affected by major eye diseases such as macular degeneration and glaucoma (3,4). Glaucoma is a neurodegenerative disease that’s increasingly prevalent among older individuals (5). Its main cause is heavily tied to the eye’s internal pressure and damage to certain nerve cells (6). Recent research has broadened our understanding of glaucoma, revealing that its neuronal damage can extend downstream to other structures of the visual system (7)

Pathology of Glaucoma

The eyes maintain their shape by continuously making fluids that help keep the eye’s internal pressure (intraocular pressure) stable (6). In a healthy eye, this fluid—known as aqueous humor—gets recycled and drains through a specialized angle; new aqueous humor would flow through to replenish it (6). However, the drainage angle can be blocked in several ways: tissue damage, scarring from abnormal blood vessels, or the iris being too close to the drainage angle (8). When the drain is impaired, fluid builds up, increasing the pressure and damaging the optic nerves (6).

These optic nerves contain retinal ganglion cells (RGCs) that are located in the inner retina (9). As light passes through the eye and activates the photoreceptors, the RGCs are the only cells capable of transmitting a neural impulse—or “signal”—to the brain via their axons, the part of the neuron that propagates this signal out of the eye (9). Prolonged elevated intraocular pressure can compress these optic nerves (10). This leads to the region where the RGC axons exit the eye—the lamina cribrosa—to undergo severe structural changes that alter the neurons’ signal transmission, further impairing visual function (10).

Beyond the Eyes

Damage to the RGCs can produce cascading effects along the visual pathway, which includes the lateral geniculate nucleus (LGN) and the visual cortex. This process is known as trans-synaptic degeneration (7,10). All incoming motor and sensory information must pass through the thalamus within the brain before being directed to its final destination (11). The LGN, one of the relay centers in the thalamus, receives direct input from the projecting RGC axons and is organized into six layers containing two main types of neurons: magnocellular (M cells) and parvocellular (P cells) (7). M cells convey motor visual information, whereas P cells transmit color information, specifically red and green (7). From the LGN, the integrated signals are relayed to the primary visual cortex (V1) via nerve fibers known as optic radiations (10). V1 itself is also organized into six distinct layers that process input from the LGN and other cortical regions (10).

A defining feature of glaucoma is disruption of the anterograde and retrograde axonal transport (12). Antegrade transport directs “cargo” (i.e. proteins, vesicles, etc.) away from the cell body and toward the output site, whereas retrograde transport directs them back toward the cell body (13). These mechanisms rely on motor proteins to deliver essential molecules and nutrients (neurotrophic factors) necessary for neuronal survival (10,12). Anterograde degeneration originates from damage at the retinal level, subsequently affecting the downstream visual pathway (7). Conversely, retrograde degeneration begins within higher visual areas, such as the primary visual cortex in the occipital lobe, and propagates back toward the retina (7). These, in turn, result in trans-synaptic degeneration, where loss of input from one neuron induces damage in connected neurons across synapses (10).

Deprivation of incoming nutrients can cause a cell to lose structural integrity and undergo atrophy, as seen in both the M and P cells within the LGN (10). P cells show significant shrinkage correlated with RGC loss, while M cells experience both pronounced atrophy and cell loss (10). As a result, individuals with glaucoma exhibit a measurable reduction in their LGN volume on MRI scans (14). Because P and M cells provide direct input into the visual cortex—which contains a far greater number of neurons—V1 also shows a corresponding decrease in cortical thickness, reflecting widespread neurodegenerative changes along the visual pathway (7,10).

Conclusion

The disruption of the visual pathway manifests in symptoms of blurry vision and eye pain (6). More importantly, glaucoma also delays visual processing, particularly in tasks involving object and animal categorization (15). This highlights that glaucoma-related damage isn’t just restricted to the eye, but also involves the central visual pathway and its first- and higher-order structures—the LGN and the visual cortex (7). With a broader perspective, this reflects a theme shared by many neurodegenerative diseases: damage localized to one region can reverberate throughout the brain, demonstrating the interdependence of neural connections underlying human perception.