When navigating a complex, three dimensional environment primates, including humans, must constantly move their eyes to ensure that objects of interest activate the foveae of both eyes. For children with infantile strabismus syndrome the eyes are chronically misaligned, which makes normal binocular vision impossible. Persistence of this condition can lead to lasting impairments of visual function, including amblyopia, and impaired depth perception. Oculomotor abnormalities include a lack of disparity vergence, saccade disconjugacy, latent nystagmus, and a nasalward bias of smooth pursuit gain. Existing treatments are successful in some patients but, in others, improvements in eye alignment prove to be transient. Monkeys with strabismus experimentally induced in infancy show visual and oculomotor abnormalities that closely match those found in human children. In recent years, work with these nonhuman primate models has provided compelling evidence that prolonged disturbance of binocular vision in infancy alters the development of neural circuits serving vision and eye movements. Over the past several years we have found clear evidence of abnormalities affecting several brainstem oculomotor regions, including paramedian pontine reticular formation, abducens nucleus, supraoculomotor area, nucleus prepositus hypoglossi (NPH), and the interstitial nucleus of Cajal (INC). In pattern strabismus, the horizontal and vertical misalignments vary with eye position along the orthogonal axis. We have found preliminary evidence that the neural basis of pattern strabismus involves abnormal crosstalk between brainstem pathways that produce the horizontal and vertical components of eye movements. Our studies are guided by the overarching hypothesis that loss of binocular vision during a sensitive period in early postnatal life leads to a cascade of abnormalities that affect both visual and oculomotor areas of the brain. At present, however, critical brainstem oculomotor regions have not been or only incompletely studied in strabismus, which makes it very difficult to test specific developmental etiological hypotheses. We will use a combination of single unit recording and microstimulation to elucidate the relationship between brainstem abnormalities and the oculomotor symptoms of infantile strabismus syndrome.
The infantile strabismus syndrome affects at least 3% of children born in the United States and is characterized by a chronic misalignment of the eyes. This disorder can lead to significant, permanent impairment of visual function, including impaired depth perception, amblyopia and impaired motion perception. Our studies are designed to identify neurological abnormalities that interfere with treatment.
| Pallus, Adam C; Walton, Mark M G; Mustari, Michael J (2018) Activity of near response cells during disconjugate saccades in strabismic monkeys. J Neurophysiol : |
| Pallus, Adam C; Walton, Mark M G; Mustari, Michael J (2018) Response of supraoculomotor area neurons during combined saccade-vergence movements. J Neurophysiol 119:585-596 |
| Walton, Mark M G; Mustari, Michael J (2017) Comparison of three models of saccade disconjugacy in strabismus. J Neurophysiol 118:3175-3193 |
| Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome et al. (2017) Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome. J Neurophysiol 118:280-299 |
| Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji et al. (2016) Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys. Invest Ophthalmol Vis Sci 57:3168-80 |
| Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M et al. (2015) Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment. Invest Ophthalmol Vis Sci 56:3484-96 |
| Walton, Mark M G; Mustari, Michael J; Willoughby, Christy L et al. (2015) Abnormal activity of neurons in abducens nucleus of strabismic monkeys. Invest Ophthalmol Vis Sci 56:10-9 |
| Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M et al. (2015) Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates. Invest Ophthalmol Vis Sci 56:3467-83 |
| Walton, Mark M G; Mustari, Michael J (2015) Abnormal tuning of saccade-related cells in pontine reticular formation of strabismic monkeys. J Neurophysiol 114:857-68 |
