Damage to Eye Movement Center Neurons of the Superior Colliculus in Experimental Primate Glaucoma

Abstract

Purpose: : To investigate whether superior colliculus neurons of the brain are damaged in experimental primate glaucoma by evaluating their pre-synaptic input and post-synaptic dendrites.

Methods: : Macaque monkeys with unilateral experimental glaucoma (n=6) were compared to normal controls (n=7). Optic nerve fibre loss in glaucoma ranged from 29% to 100%. Superior colliculus specimens were cryoprotected, frozen and cut. Sections were double-labelled for vesicular glutamate transporter 2 (VGluT-2; Synaptic Systems), a marker for pre-synaptic glutamatergic RGC terminals, and microtubule-associated protein-2 (MAP-2; Sigma), a dendrite marker. Using confocal laser microscopy, images were captured in a masked fashion, and percent supra-threshold area was measured as an index of immunofluorescence intensity (Image J software, NIH). The glaucoma group was compared to the control group using a t-test.

Results: : In the glaucoma group, mean axon loss was 44.0±43.4%. VGluT-2 intensity index in the superior colliculus was significantly reduced in glaucoma compared to controls (0.011±0.003% vs. 6.359±1.657%, mean ±SEM; p< 0.05). MAP-2 intensity index was also significantly reduced in glaucoma compared to controls (0.239±0.153% vs 1.659±0.443%; p<0.05).

Conclusions: : Reduced glutamate transporter was observed where RGCs terminate on the superior colliculus. Disrupted MAP-2 protein in superior colliculus neuron dendrites were also observed in experimental primate glaucoma. These major neurochemical changes in pre- and post-synaptic elements of the superior colliculus responsible for saccadic eye movements, point to possible eye movement deficits in patients with glaucoma.

Keywords: intraocular pressure • ganglion cells • superior colliculus/optic tectum