Muscle spindles in extraocular muscles of human infants.

The capacity of muscle spindles in adult human extraocular muscles (EOM) to provide effective proprioception was questioned on the grounds of their peculiar morphology. Their appearance could be attributable to ageing and to test this possibility examples of infant muscle spindles have been examined. Forty encapsulated structures from five extraocular muscles removed post mortem from 4 infant patients aged 6 days, 5, 23 and 30 months were examined by means of light microscopy using serial transverse sections. Seven of them were identified as false spindles. The remaining 33 structures, identified as spindles, contained a total of 175 intrafusal fibres varying from 2 to 12 (mean: 6) in each. 130 of these fibres (74.3%) were of nuclear chain type. Unequivocal evidence of bag fibres was not found. Spindles lacked or had a limited equatorial expansion, and the inner capsule was incomplete and irregularly shaped. 45 (25.7%) of the intrafusal fibres had extrafusal features with large diameters, peripherally placed nuclei, no equatorial modification and without associated sensory nerve terminals. Serial sections revealed that a majority of the nuclear chain fibres were interrupted, fragmented or terminated abruptly, and most spindles contained at least one incomplete fibre. These observations show that the atypical features observed in adult human EOM spindles are also present in infants and are therefore not attributable to ageing.

Myotendinous nerve endings in human infant and adult extraocular muscles.

Myotendinous nerve endings in extraocular muscles of some mammals consist exclusively of palisade nerve endings incorporated in myotendinous cylinders. There is evidence for a similar form in man, some doubt remains. The objectives of the present study were to examine the structure and distribution of nerve endings in extraocular muscles of infant and adult human material. Muscles from five infants and six adults aged 3 days to 90 years were prepared for light and electron microscopy. Nerve endings were sparse in a 4-year-old and none were present in the muscles of younger donors. They were present in all adult samples. One group of nerve endings branched from single recurrent nerve fibers and were distributed in the encapsulated tendon of single Felderstruktur muscle fibers. Terminals were varicose and shared certain characteristics of known sensory endings and were similar to those of myotendinous cylinders except that none formed neuromuscular junctions. In other myotendinous complexes capsules were fragmented and nerve endings were dispersed in tendon common to two or more muscle fibers. In the myotendon of two adult donors, a further group of endings issuing from non-recurrent nerves were unencapsulated and distributed randomly in tendon. The frequency of nerve endings varied across myotendon and in some instances, most marked in one case, large areas lacked nerve endings. Golgi tendon organs were not present. The terminals having features characteristic of sensory endings suggest a proprioceptive function, which is apparently unavailable in infancy. In mature muscles, the irregular distribution and variety of terminal form cannot be equated with those found in extraocular muscles of animals. We suggest that these features reflect an aberrant development and conclude that their capacity to fulfil an effective proprioceptive role is open to question.

Extraocular muscle proprioceptors and proprioception.

Uncertainty of the roles of proprioception and efference copy in visual spatial perception persists. Proprioception has won back some support recently mainly on the evidence gained from physiological experiments in man, and rather than being mutually exclusive, the two mechanisms have been presented as collaborating. Another view supported by human and animal experiments states that current visual spatial perception may be served by efference copy whereas proprioception is responsible for temporal adaptations of the system. Certain characteristics of visuomotor cells of the monkey cortex can be explained assuming an efference copy input. Anatomical data from different sources are not easily reconciled. Disagreement about the nerve pathway of muscle afferents weakens arguments based on the results of open loop experiments involving nerve lesions in monkeys. The assumed presence of Golgi tendon organs in human extraocular muscles is no longer tenable and instead, palisade endings similar to those of cats and monkeys and other, irregular nerve endings are described. But man differs in having a limited and patchy distribution of neurotendonous endings and moreover, they may develop only after infancy. The allocation of a sensory function to palisade endings in myotendinous cylinders appears secure, at least in cats. Detailed examination of muscle spindles in man reveals anomalies of structure sufficient to question their capacity to provide useful proprioceptive information. One of the anomalies is the atrophy of intrafusal muscle fibres, present in both infant and adult muscles, and it is proposed that the redundant sensory endings, which do not appear to degenerate, search for new targets and may account for the random presence of tendon nerve endings. These observations place the role of proprioception in human extraocular muscles in jeopardy; they are unsupportive of the recent physiological studies and favour efference copy.

Sensory innervation of conjunctival lymph follicles in cynomolgus monkeys.

PURPOSE: The importance of neuroregulation of immunoresponsiveness is recognized, but little is known of the innervation of conjunctival follicles. The access and distribution of nerves in follicles of the palpebral conjunctiva were therefore studied and those of trigeminal nerve origin distinguished. METHODS: Serial sections of follicles were prepared for light and selected sections for electron microscopy. Intracranial lesions were made in ophthalmic or both ophthalmic and maxillary nerves several days before fixation in three of the six monkeys used and their distribution in follicles identified by induced degeneration. RESULTS: Fine nerves penetrated follicles and terminated on arterioles, smaller blood vessels, and rarely on high endothelial venules. Other nerve branches entered the follicle parenchyma, conducted, and terminating in fine reticular fibers. Many terminals were identified as autonomic on morphologic grounds. Few terminals were in direct contact with lymphocytes and none were found in germinal centers. Other fibers terminated in the follicle associated epithelium. A large fraction of the nerve displayed degenerative changes after lesions and epithelial terminals were no longer present. CONCLUSIONS: Nerve distribution is mostly similar to that found in other lymphoid organs with the exception of the epithelial terminals, which are described for the first time in mucosa-associated lymphoid tissue and identified as sensory. Because epithelial terminals virtually were absent from the surrounding unspecialized epithelium, it is likely that those of the follicular epithelium have a specific immune system-related function. They may represent a follicle-alerting mechanism to surface stimuli.

Peripapillary venous drainage from the choroid: a variable feature in human eyes.

AIMS/BACKGROUND: Drainage of blood from the choroid is thought to occur exclusively through the vortex veins in the absence of a venous equivalent of the posterior ciliary arteries. A chance observation in the peripapillary region of the choroid, inconsistent with this concept, suggested that the subject required review. METHODS: Ten nerve heads from 10 individuals were examined histologically using interrupted serial resin sections. They were obtained from eyes free of posterior segment pathology. RESULTS: Peripapillary veins varying in number and size were present in seven preparations and none in the other three. All veins penetrated the sclera from the choroid close to the optic nerve head and entered the pia mater directly, receiving small veins from the laminar and postlaminar nerve head. No other locations of posterior venous penetrations of the sclera were found. This is the first description of these vessels in normal eyes; they are named 'choroidopial veins'. CONCLUSIONS: Choroidopial veins represent a minor and inconstant route for blood drainage from the choroid, with a role in optic nerve head circulation.

Innervation of the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey: a retrograde fluorescent tracing study.

Retrograde fluorescent transport of Fast Blue (FB) and Diamidino Yellow (DY) was used to study the localisation of neurons that innervate the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey. Labelled cell bodies of sensory neurons including a few double labelled cell bodies were found in the ophthalmic part of the ipsilateral trigeminal ganglion. Labelled cell bodies of the sympathetic neurons including a few double labelled cell bodies were located in the middle and cranial part of the ipsilateral superior cervical ganglion, with a few in the contralateral ganglion. Labelled cell bodies of the parasympathetic neurons were all found in the ipsilateral pterygopalatine ganglion and randomly distributed. Neurons were disposed in the opthalmic part of the trigeminal and superior cervical ganglia, whereas parasympathetic neurons were distributed randomly. Cells of the nodose, ciliary, geniculate, otic and first 3 spinal ganglia were unlabelled. Tracing FB and DY from the palpebral conjunctiva and superior tarsal muscle respectively, revealed double labelled neurons in the trigeminal and superior cervical ganglia, probably indicating the presence of collaterals of axons serving both the palpebral conjunctiva and the superior tarsal muscle.

Trigeminal innervation of the scleral spur in cynomolgus monkeys.

Degeneration induced by intracranial section of the ophthalmic branch of the trigeminal nerve was used as a marker to trace the ocular passage and termination of fibres in ocular filtration angle structures of 3 cynomolgus monkeys. Fine supraciliary nerves branched from precorneal nerves as they entered the sclera from the uvea, passed forwards radially in the lamina fusca, entered the scleral spur, turned circumferentially and terminated. Many of the fibres were degenerated. Other less numerous branches advanced in the ciliary muscle close to the lamina fusca and were distributed either to the spur or to the trabecular meshwork. Spur fibres were approximately 4 times as numerous as trabecular fibres. The position, arrangement and ophthalmic identity of most of the spur terminals suggest a capacity to record tension produced by ciliary muscle contraction.

Touch sensitivity of the eyelid margin and palpebral conjunctiva.

Using a slit-lamp biomicroscope mounted Cochet-Bonnet aesthesiometer, the touch sensitivity of the eyelid margin and palpebral conjunctiva was determined for both upper and lower lids in 30 subjects. Thresholds for the occlusal surface of the lid, the marginal angle and the middle of the tarsus were measured centrally. A significantly higher touch sensitivity was found for the marginal zone compared with the occlusal surface, and tarsal conjunctival sensitivity was substantially the lowest. The occlusal and marginal zones of the lower lid displayed a significantly higher touch sensitivity than the upper lid but the tarsal sensitivity of the two lids was similar. The sharp peaking of sensitivity at the leading edge of each eyelid provides a mechanism for the detection of superficial foreign bodies and presumably augments the protective role of the cornea. A large inter-subject variation in marginal touch sensitivity was found which may explain individual variation in contact lens adaptation.

Investigation of limbal touch sensitivity using a Cochet-Bonnet aesthesiometer.

Following the observation of complex sensory receptors concentrated within the palisade zone of the human conjunctiva, this study sought to measure limbal touch sensitivity using a Cochet-Bonnet aesthesiometer. Touch sensitivity was found to be significantly higher in the palisade zone compared with the adjacent conjunctiva. A comparison between temporal and inferior limbus showed a greater median sensitivity for the temporal zone. There was a significant reduction in touch sensitivity with age, but not with iris colour or contact lens wear. These data, showing a higher touch sensitivity for the palisade zone, provide indirect evidence for a role of complex nerve endings in mechanoreception.

Distribution of otic postganglionic and recurrent mandibular nerve fibres to the cavernous sinus plexus in monkeys.

The distribution of dorsal rami of the otic ganglion was traced on one or both sides of 1 rhesus and 15 cynomolgus monkeys using interrupted serial sections. From 15 to 24 fine rami containing unmyelinated and small myelinated nerve fibres entered the cranial cavity with the mandibular nerve through the foramen ovale. Most rami contributed to a plexus positioned in the crotch of the mandibular and maxillary nerves adjacent to the trigeminal ganglion. The plexus was augmented by an accessory otic ganglion. Rami then continued dorsally on each side of or through the maxillary nerve and joined the cavernous sinus plexus. The pathway described probably gives otic parasympathetic fibres access to the cerebral arteries and may share a wider distribution in common with other nerves contributing to the cavernous sinus plexus.

The internal carotid artery has a sleeve of increased innervation density within the cavernous sinus in monkeys.

The numerical density of nerve terminals of the internal carotid artery was measured using interrupted serial sections and compared with densities sampled from the major cerebral arteries of cynomolgus and rhesus monkeys. In its course through the carotid canal and the foramen lacerum the artery received few terminals. Nerve terminal density increased substantially within the cavernous sinus in 13 of 19 animals, reaching a peak shortly before emerging to join the circle of Willis. The density dropped rapidly on leaving the sinus. The increase was present in both species and rose to a mean nerve terminal density at least ten times that of any other artery measured. In 6 monkeys terminal incidence was unchanged through the sinus. The possible relevance of the nerve terminal sleeve to cerebral vasodynamics and to vascular head pain is discussed.

The structure of corpuscular nerve endings in the limbal conjunctiva of the human eye.

Corpuscular nerve endings were found to be numerous within a narrow, 1.00 mm wide, annular zone of limbal conjunctiva, located approximately 0.5 mm from the corneoscleral margin. A light and electron microscopic study was carried out on these nerve endings found within samples of human eye-bank material. Corpuscular endings were found immediately under the epithelium, often within the stromal elevations which make up the limbal palisades of Vogt. They were round to oval in shape, and varied in size, with a mean maximum diameter of 30 microns. The afferent nerve fibre lost its myelin sheath soon after entry, and subsequently branched to give rise to a variable number of axon terminal varicosities, which were characterised by an accumulation of mitochondria. Neural elements within the nerve ending were invested by the cytoplasmic lamellae of Schwann-like accessory cells. The corpuscle was demarcated from the surrounding connective tissue by a delicate fibrocyte capsule. The corpuscular nerve endings described here in the conjunctiva share features common to corpuscles found in other mucosae. The function of such complex sensory nerve endings is as yet unknown, but the possibility that they represent receptors for particular sensory modalities should be explored.

Accommodation and the nerve pathway to the ciliary muscle: a review.

Evidence has accumulated recently which challenges the conventional description of the parasympathetic division of the oculomotor nerve pathway to intraocular smooth muscles. It is claimed that the pathway from the midbrain to the ciliary muscle is direct and uninterrupted by a synapse in the ciliary ganglion. A similar, separate claim has been made regarding the innervation of the sphincter muscle of the iris. The weaknesses in the arguments supporting the revised versions are discussed in this review and they are rejected in favour of the conventional pathway.

Golgi tendon organs in the proximal tendon of sheep extraocular muscles.

Sheep extraocular muscles were prepared for light and electron microscopy and their proximal tendons searched for Golgi tendon organs (GTO). An extensive aponeurotic lamina on the orbital surfaces contained numerous GTO 250-1350 microns in length with characteristic terminal form and relationship with collagen. They differed from usual GTO structure in containing large fluid-filled spaces dividing collagen into several well separated compartments and a muscle fiber entered and terminated in about one third of the receptors. The fibers, Felderstruktur in type, often penetrated deep within tendon organs, and in a few instances two or more fibers entered. This feature is shared by the rare GTO of monkey extraocular muscles. That the presence of GTO in the proximal tendons of extraocular muscles is previously unrecorded may be attributed to the practice of restricting attention to the long distal tendons. The possibility that receptors may be so placed in other species warrants further work especially in those purported to lack any receptor.

The fine structure of human extraocular muscle spindles and their potential proprioceptive capacity.

Twenty seven muscle spindles from six extraocular muscles removed following ocular enucleation from patients aged 58, 76 and 74 years were examined throughout all or most of their length by means of light and electron microscopy using serial transverse sections. Five others were prepared in longitudinal section. Twelve spindles of the superior rectus muscle from three sheep orbits were studied in a similar manner to provide a comparison. The human spindles contained a total of 90 (42%) nuclear chain and 5 (2%) nuclear bag fibres with the usual complement of sensory endings, and 120 (56%) fibres were anomalous with continuous, unattenuated myofibrils throughout their length, a constant width and peripherally placed nuclei. Eight anomalous fibres received sensory terminals similar in form to those of chain and bag fibres. Most (26) spindles contained at least one chain and one anomalous fibre. The periaxial space was limited or absent and the inner capsule was often segmented and in contact with the outer capsule. Abrupt termination of some chain fibres including several with one pole missing, together with evidence of fibre fragmentation and other structural anomalies, were indicative of degeneration. Eight further encapsulated fibre groups were identified as false spindles containing only anomalous fibres; associated nerves failed to terminate in the encapsulations. Sheep spindle content was of regular form, all spindles containing several chain and at least one bag fibre enclosed by an inner capsule and surrounded by a substantial periaxial space equatorially. The human extraocular muscle spindles have lost, either by aging or phylogenetically, the privilege of contractile chambers isolated by a fluid periaxial space from extrafusal fibre activity and sensory terminals are subject to the direct mechanical influences of anomalous intrafusal fibres. These, and the other departures from normal structure described, must jeopardize monitoring of muscle activity in the manner normally attributed to spindles and their capacity to provide useful proprioceptive information is questionable.

A subepithelial elastic lamina in the palpebral conjunctiva of monkeys.

Eyelids from ten cynomolgus monkeys were sectioned in a variety of orientations and the conjunctival layer examined by light and electron microscopy. An elastic lamina composed of a mesh of mature elastic fibres was present in the palpebral conjunctival stroma adjacent to the epithelium covering the area of the tarsal plate and extending to the lid margin. Mesh fibres orientated at or close to right angles to the lid margin were thicker and denser than the transverse and oblique fibres linking them. The elastic lamina was most substantial in the marginal conjunctiva bridging the interval between the tarsal plate and the mucocutaneous junction where it terminated abruptly. In this position the area occupied by the elastic mesh exceeded that of the mesh spaces. Dense collagen bundles enclosed the lamina, infiltrating the mesh spaces and attaching the lamina firmly to the tarsal plate. In the marginal zone thick elastic fibres branched forward from the lamina in a brush-like fashion penetrating the relatively soft marginal eyelid tissue obliquely between tarsal gland ducts, while other finer, more numerous fibrils passed backwards attaching the lamina to the basement membrane of the epithelium. The organisation of the elastic lamina suggests that the tension generated would act to pull the lid margins towards the surface of the eye. Production of a regular thin tear film during lid retraction following a blink is facilitated by this action.

Distribution and termination of trigeminal nerves to the cerebral arteries in monkeys.

Wallerian degeneration was used to study the contributions of the first and second divisions of the trigeminal nerve to cerebral arterial innervation in the cynomolgus monkey. Animals were killed by intracardiac perfusion of fixative three to seven days after left ophthalmic or maxillary neurotomy or a combination of both, using three animals for each procedure. Cerebral arteries were dissected, removed and prepared for light and electron microscopy. The anterior vessels of the circle of Willis received nerve fibres, distributed via the internal carotid artery, from the ipsilateral ophthalmic branch of the trigeminal nerve and a small maxillary contribution was also observed in some animals. The posterior vessels were supplied from the same trigeminal source but by a different route, the nerves moving onto the basilar artery bilaterally or unilaterally via the recurrent nerve of the cavernous plexus using the abducent nerve for access. From the basilar, fibres distributed to both posterior cerebral arteries. Augmentation of the vascular nerve supply apparently from branches of the vagus and/or hypoglossal nerves was noted but otherwise unexamined. Trigeminal terminals were found on all vessels of the circle of Willis and their distal branches throughout the thickness of the adventitia, often lying close to the media but never contacting smooth muscle cells. These observations are consistent with results from other studies employing neurohistochemical and tracer techniques in subprimates. Comparison of operated and control material failed to reveal any distinctive features of terminals attributable to a trigeminal source.

The tentorial nerve in monkeys is a branch of the cavernous plexus.

The origin and content of the tentorial nerve in cynomolgus and rhesus monkeys were studied using light and electron microscopic inspection of interrupted serial sections of the trigeminal/cavernous sinus region combined with selective nerve degeneration. The nerve was invariably a branch of the cavernous plexus rather than a branch of the trigeminal ganglion or ophthalmic nerve as described in earlier reports. The cavernous plexus branch forming the tentorial nerve joined and passed back in the trochlear nerve while it remained in the lateral wall of the cavernous sinus, then left the trochlear to be distributed in the tentorium cerebelli. It was composed of trigeminal fibres mainly from the ophthalmic division together with sympathetic fibres from the superior cervical ganglion. The source of another group of unmyelinated fibres was unidentified but they are likely to be parasympathetic.

Trigeminal nerve pathways to the cerebral arteries in monkeys.

Two or three or sometimes more fine intracavernous branches were traced from the ophthalmic nerve using serial section reconstruction and induced nerve degeneration. They joined the cavernous plexus and were distributed forward with autonomic nerves to the adventitia of the internal carotid artery, emerging from the sinus with the artery. A strong recurrent branch from the plexus joined the abducent nerve, passed back and left the nerve at pontine level to innervate the basilar artery and the caudal circle of Willis. The recurrent nerve was absent from one side of two animals and showed asymmetry in others. No branch issued intracranially to the plexus from the maxillary nerve, but in the pterygopalatine fossa the orbitociliary branch of the maxillary nerve gave off one or two filaments that re-entered the cranial cavity through the medial infraorbital fissure and joined the cavernous plexus. Their content augmented the ophthalmic afferent distribution. All plexus branches with trigeminal fibres also contained autonomic fibres. The results show, firstly, that the cavernous plexus consists of a mixture of sensory and autonomic nerves (sympathetic and parasympathetic) and, secondly, that afferents of the internal carotid artery and rostral circle of Willis and those to the basilar artery and caudal circle of Willis are distributed separately.