Developmental strabismus (ocular misalignment) remains one of the most prevalent clinical problems related to the visual-oculomotor system in children. In addition to horizontal eye misalignment, a host of other oculomotor disturbances are associated with strabismus and despite considerable work, the mechanisms underlying some of the unique oculomotor properties associated with the condition are unknown.
In aims 1 and 2 of this proposal, we focus on addressing how strabismic subjects orient their eyes to visual and non-visual target stimuli within their environment. This is especially interesting in the strabismic subjects because of their ability to choose either of their eyes to acquire the target. Fixation preference is thought to be driven by visual suppression of information from portions of the retina. However, eye movements are also made to acquire non- visual (eg: auditory) targets. What happens to fixation preference and fixation-switching behavior in strabismus when no visual stimulus is available? Aim 1 involves comparative studies of fixation switch and fixation preference when the stimulus to the strabismic animal is either visual or auditory.
In aim 2, we propose single unit recording studies of neurons in the superior colliculus (SC) to determine their role in fixation-switch behavior in response to the visual or auditory stimuli. The SC is chosen as the target of investigation because of its reported role in target selection and its role in orienting to visual and auditory stimuli and in multisensory integration.
Aim1 and Aim 2 studies will be performed in juvenile rhesus non-human primates previously induced with a sensory form of strabismus by rearing them under special viewing conditions (optical prism rearing) for the first four months of their life.
In Aim 3, we propose to develop a new non-human primate strabismus model that utilizes loss of eye muscle proprioception due to sectioning of the ophthalmic division of the trigeminal nerve in infancy. The motivation to develop a new model is that despite considerable work, the mechanisms underlying the development of strabismus, especially in those patients where there is no obvious loss of binocular vision or extraocular muscle disruption, are unknown. Our hypothesis is that intact eye muscle proprioception is also needed for development of proper ocular alignment. We will investigate the longitudinal development of eye alignment in these animals and compare proprioceptive loss strabismus to that occurring due to loss of binocular vision (optical prism strabismus). In summary, each of the specific aims in this project is likely to significantly advance our understanding of strabismus mechanisms and the neural circuitry underlying some of its properties. Moreover, this project has the potential to help guide the development of rationally based therapies.

Public Health Relevance

Ocular misalignment (strabismus) is a developmental disorder that affects a significant number of children born every year in the United States and around the world. A better understanding of neural and peripheral mechanisms that are affected in the different forms of strabismus will help develop rationally based therapy. This project will a) combine various physiological methods and behavior investigation in an animal model to investigate how gaze is re-oriented to visual and non-visual (auditory) stimuli in strabismus b) develop and study a novel animal model (proprioceptive loss strabismus model) to shed new insight onto central and peripheral correlates to disruption of eye alignment in strabismus.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
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Araj, Houmam H
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University of Houston
Schools of Optometry/Opht Tech
United States
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Upadhyaya, Suraj; Meng, Hui; Das, Vallabh E (2017) Electrical stimulation of superior colliculus affects strabismus angle in monkey models for strabismus. J Neurophysiol 117:1281-1292
Upadhyaya, Suraj; Pullela, Mythri; Ramachandran, Santoshi et al. (2017) Fixational Saccades and Their Relation to Fixation Instability in Strabismic Monkeys. Invest Ophthalmol Vis Sci 58:5743-5753
Joshi, Anand C; Agaoglu, Mehmet N; Das, Vallabh E (2017) Comparison of Naso-temporal Asymmetry During Monocular Smooth Pursuit, Optokinetic Nystagmus, and Ocular Following Response in Strabismic Monkeys. Strabismus 25:47-55
Das, Vallabh E (2016) Strabismus and the Oculomotor System: Insights from Macaque Models. Annu Rev Vis Sci 2:37-59