Glaucoma is accompanied by reduction of GABA and degraded neural specificity in the visual cortex.

Abstract

Purpose : Glaucoma affects both the eye and brain, yet it remains unclear how the neurometabolic mechanisms change with glaucoma. Here, we used proton magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) to investigate GABA and glutamate signals as well as the neural specificity in the visual cortex of our glaucoma cohort and healthy controls.

Methods : Forty-one individuals with glaucoma (65.88 ± 1.23 yrs) (mean ± S.E.M.), and twenty-three healthy controls (64.78 ± 1.63 yrs) underwent anatomical MRI, MRS and fMRI at 3 Tesla. Individuals with glaucoma were categorized to either early or advanced stage based on the mean deviation (MD) (early: MD > -6.0dB; advanced: MD < -6.0dB). We obtained the levels of GABA and glutamate from the visual cortex from MRS and acquired fMRI while subjects viewed a flickering checkerboard at the horizontal vs. vertical meridians. Subjects’ ophthalmic data was obtained using optical coherence tomography (Fig. 1).

The MRS spectra were fitted using the LCModel and normalized by creatine. The neural specificity — the dissimilarity of brain activities between different visual stimuli — was measured by calculating the Fisher’s correlation coefficient of brain activities in the visual cortex between two stimuli. Using principal component analysis, we extracted a common component from ophthalmic measures, and used it as the retina structure index. Subjects’ gray matter volume of the visual areas was measured using Freesurfer.

Results : A significant reduction of GABA levels was observed in advanced glaucoma patients compared to healthy controls (Bonferroni P=0.001; Fig. 2A). The retina structure index predicted the GABA levels after adjusting for age (P=0.020; Fig. 2B).

Similarly, the glutamate levels were significantly lower in advanced glaucoma patients compared to healthy controls (Bonferroni P=0.026) and early glaucoma patients (Bonferroni P=0.030; Fig. 2C). The retina structure index predicted the glutamate levels after adjusting for age (P=0.011; Fig. 2D).

The levels of GABA (P=0.037), but not glutamate (P=0.498) predicted the neural specificity after controlling for the levels of other metabolites, retina structure index, age, and the gray matter volume of the visual areas (Fig. 2E, F).

Conclusions : Our results suggest that reduction of GABA levels is tightly linked to degraded neural specificity in the visual cortex of glaucoma patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.