Retrolaminar Demyelination of Structurally Intact Axons in Nonhuman Primate Experimental Glaucoma

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Glaucoma is a leading cause of irreversible blindness worldwide.
• Optic nerve damage in glaucoma is characterized by the loss of retinal ganglion cell axons.
• The demyelination status of structurally intact axons in early to moderate glaucoma remains unclear.

Purpose of the Study:

• To investigate whether structurally intact retrolaminar optic nerve (RON) axons are demyelinated in a nonhuman primate (NHP) model of experimental glaucoma (EG).

Main Methods:

• Unilateral EG was induced in NHPs (n=3).
• Optic nerve heads were analyzed using scanning block-face electron microscopy (SBEMR) and micro-computed tomographic reconstructions (µCTRs).
• Myelin onset distance (MOD) from the posterior laminar surface (PLS) was measured for intact axons in EG and control eyes.

Main Results:

• MOD was significantly increased in EG eyes compared to control eyes (P < 0.0001).
• Axon loss was observed in EG eyes, ranging from -8.3% to -32.9%.
• Demyelination of intact RON axons was confirmed in EG NHPs.

Conclusions:

• Structurally intact RON axons undergo demyelination in early to moderate experimental glaucoma in NHPs.
• Further research is warranted to elucidate the functional consequences of demyelination in glaucoma.