Visual cortical γ−aminobutyric acid and perceptual suppression in amblyopia

Abstract

In amblyopia, abnormal visual experience during development leads to an enduring loss of visual acuity in adulthood. Physiological studies in animal models suggest that intracortical GABAergic inhibition may mediate visual deficits in amblyopia. To better understand the relationship between visual cortical γ-aminobutyric acid (GABA) and perceptual suppression in persons with amblyopia (PWA), we employed magnetic resonance spectroscopy (MRS) to quantify GABA levels in both PWA and normally-sighted persons (NSP). In the same individuals, we obtained psychophysical measures of perceptual suppression for a variety of ocular configurations. In PWA, we found a robust negative correlation between the depth of amblyopia (the difference in visual acuity between the amblyopic and non-amblyopic eyes) and GABA concentration that was specific to visual cortex and was not observed in a sensorimotor cortical control region. Moreover, lower levels of visual cortical GABA were associated with weaker perceptual suppression of the fellow eye by the amblyopic eye and stronger suppression of the amblyopic eye by the fellow eye. Taken together, our findings provide evidence that intracortical GABAergic inhibition is an important component of the pathology of human amblyopia and suggest possible therapeutic interventions to restore vision in the amblyopic eye through enhancement of visual cortical GABAergic signaling in PWA.

Developmental hearing loss-induced perceptual deficits are rescued by cortical expression of GABABreceptors

“…Restoring cortical synaptic inhibition may be relevant to a range of developmental disorders. For example, GABA levels in visual cortex are reduced in amblyopia and this is correlated with weaker perceptual suppression by the amblyopic eye (Mukerji et al, 2022). By directly comparing the impact of restoring Gabra1 and Gabbr1b protein expression we have shown that this effect was only achieved by upregulating GABA B receptor-mediated inhibition.…”

Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats

“…The recovery of VEPs observed after MI may also involve an alteration of inhibition that could relieve an imbalance in interocular perceptual suppression thought to contribute to the deficits in vision linked to amblyopia ( Harrad and Hess, 1992 ; Sengpiel et al, 2006 ; Li et al, 2011 ; Hess and Thompson, 2015 ; Mukerji et al, 2022 ). The shift in interocular suppression may originate from a modification of the number or size of inhibitory synapses that follow a period of MD ( Chen et al, 2011 ; van Versendaal et al, 2012 ), and which, along with a reduction in inhibitory drive ( Kuhlman et al, 2013 ), may produce a weakening of inhibitory synapses serving the deprived eye.…”

Perceptual Center-Surround Contrast Suppression in Adolescence

“…Changes in center-surround contrast suppression have been associated with altered neurotransmitter levels in human visual cortex, notably the major inhibitory neurotransmitter GABA. 31 , 63 , 64 There is also evidence that other mechanisms play a role in determining center-surround suppressive effects, such as withdrawal of excitation not primarily driven by GABA-mediated inhibition 27 or cholinergic system involvement. 28 , 29 There is some evidence of discrete changes in components of excitatory (glutamate) and inhibitory (GABA) neurotransmitter systems that could impact on the circulating neurotransmitter levels—for example, receptor expression levels, synthesis, vesicular transport, and release of neurotransmitter.…”