Understanding the development of amblyopia using macaque monkey models

Abstract

Amblyopia is a sensory developmental disorder affecting as many as 4% of children around the world. While clinically identified as a reduction in visual acuity and disrupted binocular function, amblyopia affects many low- and high-level perceptual abilities. Research with nonhuman primate models has provided much needed insight into the natural history of amblyopia, its origins and sensitive periods, and the brain mechanisms that underly this disorder. Amblyopia results from abnormal binocular visual experience and impacts the structure and function of the visual pathways beginning at the level of the primary visual cortex (V1). However, there are multiple instances of abnormalities in areas beyond V1 that are not simply inherited from earlier stages of processing. The full constellation of deficits must be taken into consideration in order to understand the broad impact of amblyopia on visual and visual–motor function. The data generated from studies of animal models of the most common forms of amblyopia have provided indispensable insight into the disorder, which has significantly impacted clinical practice. It is expected that this translational impact will continue as ongoing research into the neural correlates of amblyopia provides guidance for novel therapeutic approaches.

Neural sources of letter and Vernier acuity

“…Vernier acuity is believed to be limited by cortical mechanisms because Vernier acuity can be rendered constant across the visual field if the stimuli are scaled by estimates of the cortical, rather than retinal magnification factor 23 . The loss of letter acuity that is the hallmark of amblyopia is the result of damage to cortical mechanisms [28][29][30][31] , so the two share a dependence on cortical processing, but this is not a strong mechanistic constraint in and of itself.…”

“…Grating acuity falls off relatively slowly in the periphery and its rate of fall-off is consistent with sampling limits on resolution set by the retina 23 . The much steeper dependence on eccentricity shown in both Vernier and certain forms of letter acuity [24][25][26][27] suggests that additional constraints are imposed in visual cortex, which is also the primary site of amblyopia [28][29][30][31] .…”

Contributions of nonhuman primate research to understanding the consequences of human brain injury during development

“…Contrary to the widely held view that early lesions can rescue cognitive functions through plastic changes and reorganization, it is now recognized that some early lesions, even those that are unilateral, can have widespread effects by not only impeding circuit structure but additionally by interfering with the structure of other circuits with which they interact. This pattern of widespread structural and functional disruption is reported in both humans and NHPs (26,27).…”

International primate neuroscience research regulation, public engagement and transparency opportunities

“…Many advances in our understanding of brain function have resulted from the use of animal models and through the sharing of research outcomes, involving many species of animals, including NHPs. For example, NHP animal models helped develop successful treatments for amblyopia, which affects 4% of children around the world ( Kiorpes, 2019 ) as well as effective treatments for Parkinson's disease, which affects about 1-in-500 people over the age of 50 years living in the UK (for review see Goldberg, 2019 ). Appropriate harm/benefit analyses should be applied to proposed future international collaborations involving NHP research models, to determine the extent of the harms and how harm can be mitigated with appropriate, humane interventions and end-points.…”