Autonomic control of the eye

Abstract

The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia, and by way of sympathetic innervation from postganglionic fibers that originate from neurons in the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction, respectively. Superior cervical ganglion neurons project to the dilator pupillae muscle of the iris to control pupil dilation. Ocular blood flow is controlled both via direct autonomic influences on the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as via indirect influences on retinal blood flow. In mammals, this vasculature is innervated by vasodilatory fibers from the pterygopalatine ganglion, and by vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure is regulated primarily through the balance of aqueous humor formation and outflow. Autonomic regulation of ciliary body blood vessels and the ciliary epithelium is an important determinant of aqueous humor formation; autonomic regulation of the trabecular meshwork and episcleral blood vessels is an important determinant of aqueous humor outflow. These tissues are all innervated by fibers from the pterygopalatine and superior cervical ganglia. In addition to these classical autonomic pathways, trigeminal sensory fibers exert local, intrinsic influences on many of these regions of the eye, as well as on some neurons within the ciliary and pterygopalatine ganglia.

Figure 1

A schematic diagram showing the parasympathetic and sympathetic innervation of the eye. Neurotransmitters and neuropeptides that are generally present in postganglionic neurons are identified. *Only seen in avian studies to date. Abbreviations: ACh – Acetylcholine; ATP – Adenosine triphosphate; CG – Ciliary ganglion; EWpg – Edinger-Westphal nucleus, preganglionic; IML – Intermediolateral nucleus (cell column); NA – Noradrenaline; nNOS – neuronal nitric oxide synthase; NPY – Neuropeptide Y; PPG – Pterygopalatine ganglion; SCG – Superior cervical ganglion; SSN – Superior salivatory nucleus; VIP – Vasoactive intestinal peptide.

Figure 2

Autonomic and trigeminal ocular projections. The dotted line shows a ciliary ganglion projection to the choroid which, to date, has been shown only in birds. Line thickness indicates relative strength of projection. Abbreviations: BV - Blood vessels; CNS – Central nervous system; EWpg – Nucleus of Edinger-Westphal, preganglionic division; ICN – Intrinsic choroidal neurons; IML – Intermediolateral nucleus; NVSM – Non-vascular smooth muscle; SSN – Superior salivatory nucleus.

Figure 3

Line drawings showing the organization of EWpg and EWcp in several selected species: avian, rat, cat, monkey, and human. Representative rostral (left column), middle (middle column) and caudal (right column) sections are shown. The EWcp is indicated by light gray shading and EWpg is indicated by dark gray shading. Scattered cells located outside the nuclear boundaries are indicated by appropriately shaded circles. (From Kozicz et al., 2011) (195).

Figure 4

Three dimensional (3-D) representations of human, macaque, cat, rat and pigeon oculomotor complex, to illustrate the 3-D organization of EWpg and EWcp. The 3-D models are cut at selected points to illustrate how frontal sections through this level would look. In cases where the population is scattered, and so not contained in a discrete nucleus, dots are used. (From Kozicz et al., 2011) (195).

Figure 5

Diagram showing the location of prechoroidal SSN neurons in rat. Abbreviations: 8n, vestibulocochlear nerve; Acs7, accessory facial nucleus; das, dorsal acoustic stria; DC, dorsal cochlear nucleus; g7, genu of facial nerve; GiA, alpha part of gigantocellular reticular nucleus; icp, inferior cerebellar peduncle; m7, facial nucleus; mlf, medial longitudinal fasciculus; LPGi, lateral paragigantocellular nucleus; PPy, parapyramidal nucleus; Pr, prepositus nucleus; py, pyramid; RMg, raphe magnus; RPa, raphe pallidus nucleus; rs, rubrospinal tract; scp, superior cerebellar peduncle; Sp5, spinal trigeminal nucleus; sp5, spinal trigeminal tract; SSN, superior salivatory nucleus; ts, tectospinal tract; VeCb, vestibulocerebellar nucleus; VeL, lateral vestibular nucleus; VeM, medial vestibular nucleus. (Modified from Li et al. 2010) (210)

Figure 6

Anatomical drawing showing the parasympathetic and sympathetic innervation of the iris in primates. The bilateral projection from the retina to the pretectum is also shown. The pretectal olivary nucleus receives input from the temporal retina of the ipsilateral eye and the nasal retina of the contralateral eye. The pretectal olivary nucleus projects bilaterally to the Edinger-Westphal nucleus, which contains parasympathetic, preganglionic, pupilloconstriction neurons. The axons of these preganglionic neurons travel in the third cranial nerve to synapse upon postganglionic pupilloconstriction neurons in the ciliary ganglion. The axons of these postganglionic neurons leave the ciliary ganglion and enter the eye via the short ciliary nerves, and travel through the choroid to innervate the sphincter muscle of the iris. The sympathetic preganglionic pupillodilation neurons are found at the C8-T1 segmental levels of the spinal cord. The axons of these neurons project from the spinal cord via the dorsal roots and enter the sympathetic trunk, and then project rostrally to the superior cervical ganglion where they synapse with the postganglionic neurons. These postganglionic neurons project from the superior cervical ganglion through the neck and carotid plexus, and into the orbit of the eye. These fibers enter the eye either by passing through the ciliary ganglion and entering in the short ciliary nerves, by bypassing the ciliary ganglion and entering via the long ciliary nerves, or through the optic canal (for clarity only one of these alternative pathways is shown). Upon entering the eye, these axons travel through the choroid and innervate the dilator muscle of the iris.

Figure 7

Low power photomicrograph of a cross section of the macaque iris. The approximate location of the dilator pupillae is shown since it is not clearly evident at this magnification. Scale bar = 200 µm.

Figure 8

The response of a pupil-related EW neuron during 0.5 Hz sinusoidal modulations in light intensity and the resultant pupillary responses. The activity of the neuron is modulated sinusoidally and also shows a phase advance with respect to the pupilloconstriction. Note that the animal maintained fixation of the target for the entire period of the trial. Abbreviations: HL - Horizontal position of the left eye; VL - Vertical position of the left eye. (Scale Bar = 1mm).

Figure 9

A Nissl-stained section through the pretectum of the rhesus macaque showing the location of the pretectal olivary nucleus. Abbreviations: AQ – Aqueduct; PAG – Periaqueductal Gray; PC – Posterior commissure; PON – Pretectal olivary nucleus; NOT – Nucleus of the Optic Tract. Scale bar = 500 µm.

Figure 10

A. WGA-HRP anterograde labeling of retinal afferent terminals in the PON after intraocular injections of the tracer on the contralateral side. B. WGA-HRP retrogradely labeled neurons indicated with arrows in the PON contralateral to an injection site that included the Edinger-Westphal nucleus. Most neurons are encountered in the shell surrounding the central neuropil. Scale bars = 50 µm (Modified from Gamlin and Clarke, 1995) (115).

Figure 11

Schematic diagram of the direct and consensual pupillary light pathways in primates including humans. It is believed that the ipsilateral visual field is of cortical origin (64). Abbreviations: AQ – Aqueduct; EW - Edinger-Westphal nucleus; F – Fovea; OC – Optic chiasm; PC – Posterior commissure; PON – Pretectal olivary nucleus.

Figure 12

Photograph of melanopsin-containing ipRGCs cells in peripheral macaque retina. Scale bar = 100 µm. (Modified from Dacey et al., 2005) (72).

Figure 13

Pupilloconstriction elicited by a ten second light stimulus of 493 nm wavelength light at 14.0 log quanta/cm2/second irradiance (blue trace), and 613 nm wavelength light at 14.1 log quanta/cm2/second irradiance (red trace). Note that a 473 nm stimulus, which effectively activates the intrinsic photoresponse of ipRGCs, drives a larger pupillary response than the 613 nm stimulus (red trace), which does not effectively activate the intrinsic photoresponse of ipRGCs at this irradiance level. Also note that the pupilloconstriction induced by the 473 nm light is maintained following light cessation - this is termed the post-illumination pupil response (From Kankipati et al, 2010) (177).

Figure 14

Luminance neurons in the pretectal olivary nucleus (PON) drive the pupillary light reflex. (A) The response of a single neuron is the pretectal olivary nucleus in response to a 100 troland light stimulus. The pupillary response to the same light stimulus is shown in the trace above. (B) Electrical microstimulation at the level of the PON produces pupillary constriction, even in the absence of a light stimulus.

Figure 15

Schematic of the modified dual interaction model that accounts for the pupillary near response component of the near response triad. This model indicates that the combined output of the accommodation controller and the convergence controller drive the pupillary near response.

Figure 16

Effect of microstimulation of the EW on ocular accommodation. A shows stimulation (80 msec; 500Hz; 40 µA) producing an accommodative response with a latency of 75 msec. Accommodative velocity (ACCV) is also shown to facilitate estimation of the latency of the accommodative response. Note that, in addition to accommodation, there is an adduction of the right eye which presumably results from current spread to the nearby medial rectus motoneurons of the "C" subgroup of the right oculomotor nucleus. The stimulation also produces a small amount of convergence that is either the result of activation of the axon collaterals of near-response neurons that project to medial rectus motoneurons and presumably also to the Edinger-Westphal nucleus or stimulation of nearby medial rectus C-group motoneurons. B confirms the specificity of the microstimulation effect by showing that only accommodation is elicited when a stimulation train of shorter duration (10ms; 500Hz; 40 µA) is used. Abbreviations: HL - horizontal position of the left eye; HR - horizontal position of the right eye; VA - Vergence angle. (Scale Bar = 1 meter angle and 1 diopter). (From Gamlin et al. 1994) (118).

Figure 17

Behavior of a preganglionic EW neuron during sine wave tracking of a target moving in depth. The firing rate modulates between approximately 15 spikes/second and 25 spikes/second for the change in accommodation of 5 diopters. Note that there is a significant phase lead in the firing rate of this cell with respect to accommodation that cannot be accounted for solely by the latency between the activity of the cell and accommodation. This phase lead results from a substantial component of the firing rate being related to the dynamics of the movement. Abbreviations: HL - horizontal position of the left eye; HR - horizontal position of the right eye; VA - Vergence angle. (Scale bar is equal to 2 meter angles and 2 diopters). (From Gamlin et al. 1994) (118).

Figure 18

Response properties of a far accommodation cell in the posterior interposed nucleus during normal binocular viewing and partial dissociation of vergence from accommodation during conflict viewing. Initial VA and ACC of 1 MA and 1 D respectively in A and B. A: during normal binocular viewing, activity of this neuron decreases as a function of near response. B: response of this cell during a convergence movement similar in amplitude to that in A and an accommodative response substantially lower than that in A. This difference is best appreciated by reference to upper of 2 dashed lines that indicates accommodative response in A. For reference, lower of 2 dashed line is located at same relative level as it is in A. Note that decrease in firing rate is much less than in A. C: scatterplot and linear regression of firing rate as a function of vergence angle for normal viewing (▲) and conflict viewing (Δ). D: scatterplot and linear regression of firing rate as a function of accommodation for normal viewing (▲) and conflict viewing condition (Δ). Scale bar = 4 meter angles and 4 diopters. (From Zhang and Gamlin, 1998) (435)

Figure 19

Stimulation in the primate frontal eye fields evokes vergence and ocular accommodation. Biphasic electrical microstimulation elicited increases in vergence and ocular accommodation. Stimulation parameters; 500 Hz, 40 ms, 40 µA. AACC, average accommodation; ACC, accommodation; AVA, average vergence angle; AVV, average vergence velocity; VA, vergence angle; STIM, stimulation; VV, vergence velocity. Scale bar, 0.5 degrees, 0.5 diopters, and 5 degrees/s. (From Gamlin and Yoon, 2000) (109)

Figure 20

Scheme of adrenergic, cholinergic, and nitrergic innervations and roles of neurotransmitters in the regulation of nerve and smooth muscle functions in ciliary and ophthalmic arteries. Squares in nerve terminal and smooth muscle represent receptors. Abbreviations: NOS, NO synthase; L-Arg., l-arginine; L-Citru., l-citrulline; ATPex, exogenous ATP; PIP₂phosphatidyl inositol bisphosphate; IP₃inositol trisphosphate; DG, diacylglycerol; AC, adenylate cyclase; GC, soluble guanylate cyclase0. (From Toda et al., 1999) (391)

Figure 21

EW and SCN electrical microstimulation effects on choroidal blood flow. Solid bars indicate the timing and duration of electrical stimulation. Choroidal blood flow was measured transsclerally at a site below the superior rectus muscle in an anaesthetized animal. (Scale Bar = 50 Blood Flow Units). (Redrawn from Fitzgerald et al. 1996) (90).

Figure 22

Laser Doppler flux recordings from the anterior choroid, posterior choroid, and the nasal vortex veins during stimulation of either the superior salivatory nucleus (SSN) or the cervical sympathetic trunk (CST). All recordings were obtained from a single rat with the exception of the anterior choroid. Responses obtained from the vortex veins and anterior choroid during CST stimulation were similar to that shown for the posterior choroid. Bar indicates period of SSN stimulation (20Hz, 3V) or CST stimulation (12Hz, 30V). (From Steinle et al., 2000) (355)

Figure 23

Diagram showing the structures involved with aqueous humor formation and outflow through the trabecular meshwork and uveoscleral routes. (Figure adapted from Loewy, 1990) (216).

Figure 24

Changes in the translaminar pressure gradient after site-directed microinjection of bicuculline methiodide (•; 30 pmol/75 nL; n = 9) or saline (Δ; 75 nL; n = 10) into the DMH and PeF regions. All injections at T = 0 min. * Denotes significant difference between saline and BMI treatment groups, P < 0.05. (From Samuels et al., 2012) (326).