The organization of the eye is well designed to protect the retina, our most sensitive end organ. Environmental challenges to the eye evoke diverse reflexes that maintain ocular blood flow, intraocular pressure, pupillary diameter and lacrimation. Normal ocular reflex function depends on an intact trigeminal sensory system for full expression. Trigeminal nerves supply virtually all tissues of the eye and serve as the afferent limb for many protective reflexes mediated by the parasympathetic nervous system (PaNS). The long-term goal of this project is to determine how trigeminal and PaNS pathways interact to mediate ocular homeostasis and reflex lacrimation. Trigeminal sensory nerves that supply the eye terminate in two spatially distinct regions of the lower brainstem, trigeminal interpolaris/caudalis transition (Vi/Vc) and trigeminal caudalis/cervical cord junction (Vc/C1) regions. Although much is known about corneal sensory nerves, little is known about trigeminal nerves that supply intraocular tissues. To aid this effort, we developed a novel non-invasive stimulus paradigm that uses bright light. Bright light caused lacrimation and selectively excited intraocular trigeminal nerves and, in turn, second-order neurons at the Vc/C1 junction. Bright light-evoked Vc/C1 neural activity required a relay in accessory visual pathways, increased PaNS outflow to the eye and transmission through the trigeminal ganglion. To better understand how intraocular trigeminal nerves contribute to PaNS-mediated reflexes we will test the overarching hypothesis that intraocular and ocular surface trigeminal nerves project to common second-order neurons in two spatially distinct trigeminal brainstem regions that serve different aspects of ocular homeostasis.
Aim 1 determines the peripheral mechanism(s) in the eye that couples bright light to trigeminal brainstem activity using single neuron recording and manipulations that alter ocular blood flow and PaNS transmitter release.
Aim 2 determines the properties and efferent projections of light-responsive neurons at the Vi/Vc transition region, since currently only Vc/C1 neurons have been tested for bright light sensitivity.
Aim 3 determines the roles of the superior salivatory and Edinger-Westphal nuclei on bright light-evoked trigeminal brainstem neural responses, the main sources of PaNS outflow to the eye that affect blood flow to different ocular tissues. Tear volume and composition is monitored as an index of PaNS-mediated reflex activity. This project will provide new information on the role of trigeminal sensory nerves and CNS mechanisms that mediate ocular protective reflexes. Disruption of trigeminal-PaNS relations may contribute to symptoms in diverse conditions as dry eye disease, glaucoma and ocular hypertension that can lead to loss of visual acuity and cause discomfort.

Public Health Relevance

Maintenance of visual function after trauma, surgery or infection requires the coordinated effort of several homeostatic reflexes. Determining how the trigeminal nerve interacts with the autonomic nervous system after ocular injury may help understand how brain pathways contribute to ocular homeostasis.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-E (03))
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Araj, Houmam H
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University of Minnesota Twin Cities
Schools of Dentistry
United States
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Saito, Hiroto; Katagiri, Ayano; Okada, Shinji et al. (2017) Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach. Exp Neurol 293:124-136
Rahman, Mostafeezur; Shiozaki, Kazunari; Okamoto, Keiichiro et al. (2017) Trigeminal brainstem modulation of persistent orbicularis oculi muscle activity in a rat model of dry eye. Neuroscience 349:208-219
Katagiri, A; Thompson, R; Rahman, M et al. (2015) Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye. Neuroscience 290:204-13
Rahman, Mostafeezur; Okamoto, Keiichiro; Thompson, Randall et al. (2015) Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye. Pain 156:942-50
Khasabov, Sergey G; Malecha, Patrick; Noack, Joseph et al. (2015) Activation of rostral ventromedial medulla neurons by noxious stimulation of cutaneous and deep craniofacial tissues. J Neurophysiol 113:14-22
Katagiri, Ayano; Okamoto, Keiichiro; Thompson, Randall et al. (2014) Posterior hypothalamic modulation of ocular-responsive trigeminal subnucleus caudalis neurons is mediated by Orexin-A and Orexin1 receptors. Eur J Neurosci 40:2619-27
Rahman, M; Okamoto, K; Thompson, R et al. (2014) Trigeminal pathways for hypertonic saline- and light-evoked corneal reflexes. Neuroscience 277:716-23
Katagiri, A; Okamoto, K; Thompson, R et al. (2013) Posterior hypothalamic modulation of light-evoked trigeminal neural activity and lacrimation. Neuroscience 246:133-41
Okamoto, Keiichiro; Tashiro, Akimasa; Thompson, Randall et al. (2012) Trigeminal interpolaris/caudalis transition neurons mediate reflex lacrimation evoked by bright light in the rat. Eur J Neurosci 36:3492-9