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.

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.

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.

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.

Innervation of the conjunctiva.

A parasympathetic pathway from the facial nerve to the conjunctiva was confirmed. Many conjunctival nerve fibres were degenerated following pterygopalatine ganglion lesion in cynomolgus monkeys. Nerve terminal degeneration was found mainly in the large vessel walls and adjacent to the subepithelial capillaries. AChE positive nerve fibres of undenervated tissue, probably representing the cholinergic fibres of facial nerve origin, and sympathetic nerve terminals, identified by their small granular vesicle content, were similarly disposed in vessel walls. Hence conjunctival vessels, including capillaries, have a dual autonomic innervation. Intraepithelial terminals were sparse and no evidence of a specific goblet cell innervation was found. Human perilimbal conjunctiva displayed a similar distribution of nerve fibres to cynomolgus monkeys.

Sheathing of muscle fibres at neuromuscular junctions and at extra-junctional loci in human extra-ocular muscles.

Profuse sheathing of muscle fibres was noticed by chance when studying receptors in samples of extra-ocular muscle taken from orbits of six patients after eye enucleation or in the treatment of squint. The sheaths, previously unreported in any skeletal muscle, were examined by light and electron microscopy and their incidence determined. Muscle spindle capsules were rare by comparison. Most sheaths were found in the motor end plate band enclosing single muscle fibres and consisted of perineural epithelial cell extensions at neuromuscular junctions. Their length varied from a few to 225 micrometers, partly or fully covering neuromuscular junctions, and although limited attachments to muscle fibres were seen, the sheathed zones were probably not sealed off from the neighbouring endomysium. The incidence of sheathed neuromuscular junctions in inferior oblique muscles increased with age from none at 3 years to a maximum of 41% of the total in a specimen from the eighth decade. Mean length and thickness of sheaths also increased with age. Sheaths were far less frequent outside the motor end plate band, where most were related to grape endings of Felderstruktur fibres. Others contained from one to four muscle fibres and received their sheaths from passing nerves, but neuromuscular junctions were absent. A few of these were long, extending up to 470 micrometers. Sheath formation is evidently an expression of ageing in the perineurium, perhaps as a subsidiary feature of neuromuscular junction plasticity. The risk of confusing sheathed muscle fibres with muscle spindles is discussed.

Spiral nerve endings in human extraocular muscles terminate in motor end plates.

The long held view that spiral nerve endings in extraocular muscles are sensory, recently shown to be incorrect for monkeys, was tested in man. Muscle samples were taken from orbits of five patients after eye enucleation and prepared for light and electron microscopy. Most spiral endings terminated in the motor end plate band in several well separated clusters of boutons applied to various aspects of individual fibres, in contrast to the single group of boutons of other endings. They displayed a dapple appearance using the acetylcholinesterase technique and possessed fine structural features characteristic of motor end plates. Approximately 5% of motor end plates had spiral endings and most were sheathed by extensions from perineural epithelial cells. Hence, the spiralling of nerve fibre endings in man, as in monkeys, is a device for conveying boutons to dapple motor end plates rather than for monitoring the contraction of muscle fibres. It is suggested that muscle fibres with dapple motor end plates may be responsible for the exceptional speed of contraction of extraocular muscles.

Facial nerve distribution to the eye.

Anatomical and physiological investigations indicate that facial parasympathetic (FP) innervation to blood vessels in the eye can dilate uveal vessels and raise the intraocular pressure. There is evidence that both acetylcholine and a vasoactive intestinal polypeptide (VIP) act as neurotransmitters in this system.

Nerve terminals and epithelial cell variety in the human lacrimal gland.

Pieces of tissue taken from three human lacrimal glands were examined electron microscopically. Secretory cells varied according to the electron density and structure of their secretion granules. Secretory cells were arbitrarily categorized as light, medium or dark based on their granule content. Acini were composed of two or all three categories of cells together with myoepithelial cells and lymphocytes. A minority ogic, sympathetic terminals. The appearance of most interstitial and all parenchymal fibres was consistent with that of cholinergic, parasympathetic terminals. Parenchymal terminals were confined to ducts, terminal tubule areas and to serous (dark) cells. A large proportion of parenchymal terminals lay adjacent to myoepithelial cells in the ducts and terminal tubule regions but terminals observed among serous cells were rarely in contact with myoepithelial cells. A possible parasympathetic control of serous secretion, granule production and duct contraction and the autonomy of mucous cells is discussed.

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.

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.

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.

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.

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 fine structure of innervated myotendinous cylinders in extraocular muscles of rhesus monkeys.

Many of the myelinated nerve fibres of the distal myotendinous region of rectus muscles terminate on muscle fibre tips. The terminal expansions contain aggregated, small clear vesicles and mitochondria. Neuromuscular clefts at the contacts measure 20--40 nm and are uninterrupted by a basal lamina; the sarcoplasm opposite the contacts is unmodified. Some terminals invaginate the muscle fibre tips and others contact the sides of processes formed by splitting of the tips. The muscle fibre termination, its tendon and the nerve fibre branches are encapsulated to form an end-organ averaging 125 micrometer in length and described as a myotendinous cylinder. Approximately 350 innervated myotendinous cylinders were estimated to be present in the horizontal recti with rather fewer in the vertical rectus muscles. Many of them occur shortly before the main myotendinous junction. All muscle fibres contributing to myotendinous cylinders were identified as the compact, felderstruktur, multi-innervated variety with directly apposed myofibrils that are known to be non-twitch fibres. All felderstruktur fibre terminations examined were encapsulated but 19% of them were not innervated. The nerve terminals of myotendinous cylinders are similar to those described by Dogiel (1906) as palisade endings and it is argued that they meet the morphological criteria of sensory neuromuscular endings. Their disposition suggests a capacity to monitor felderstruktur muscle fibre contraction.

The incidence and variety of Golgi tendon organs in extraocular muscles of the rhesus monkey.

Golgi tendon organs of distal tendons of rectus muscles were traced in serial transverse sections using a light microscope and their identity confirmed with an electron microscope. One or two tendon organs were present in eight of ten muscles taken from four adult rhesus monkeys and none were present in the other two. Tendon organs were unusually small averaging 270 micrometers in length and 36 micrometers in maximum width; three of them were bifid at one or both ends and the remainder were fusiform. Some lay wholly within tendon without direct attachment of muscle fibres and in the others the tip of a single felderstruktur (slow, non-twitch) muscle fibre entered the tendon organ capsule proximally and occupied the full width. Nerve terminals of most tendon organs compared with those found in other muscles with similar organelles and variety of shape. In three tendon organs with inserted muscle fibres, however, terminals with regular profiles, larger aggregations of clear vesicles and fewer mitochondria were present. The latter type of terminal and the encapsulated filderstruktur muscle fibres are features shared by the large numbers of myotendinous cylinders present in extraocular muscles and it is argued that tendon organs and myotendinous cylinders might be of common origin. If this is the case, then the overwhelming majority of myotendinous cylinders suggests that tendon organs may be an aberrant development in extraocular muscles and of little significance in the total sensory output.

Fibre analysis of the nerve to the inferior oblique muscle in monkeys.

The nerves to the inferior oblique muscles from both sides of four rhesus and seven cynomolgus monkeys were examined by light and electron microscopy. Myelinated fibres averaged slightly over 3000 in rhesus and 2000 in cynomolgus monkeys, with a bimodal distribution of diameters in both, the lower peak being 2.5-3.0 micron and the upper 7-11 micron, the large variation of the latter applying to both species. Unmyelinated fibres were less than 10% of the total. Following intracranial ophthalmic neurectomy in five monkeys, a few unmyelinated and small myelinated fibres were degenerated in the nerve to the inferior oblique muscle (1.8% of all fibres on average). A similar proportion of fibres survived oculomotor neurectomy in three cynomolgus monkeys when the superior cervical ganglion was additionally removed. A variable number of unmyelinated fibres were degenerated in the nerve after superior cervical ganglionectomy in three cynomolgus monkeys. The experiments indicate that ophthalmic and sympathetic branches pass to the nerve to the inferior oblique muscle. The few ophthalmic nerve fibres entering the muscle appear inadequate to serve the large numbers of receptors present and therefore most of the sensory fibres probably enter the brainstem in the oculomotor nerve in both species. The sympathetic pathway to the muscle provided by its motor nerve may be augmented by others.

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.

Spiral nerve endings and dapple motor end plates in monkey extra-ocular muscles.

The suggestion that spiral nerve endings in extra-ocular muscles are sensory was tested. Spiral, serpentine and pincer-like endings were identified in extra-ocular muscles of rhesus and cynomolgus monkeys in light and electron microscopic preparations. Spiral and other complex nerve endings each terminated in the motor end plate zone as well separated clusters of boutons applied to various aspects of the muscle fibre, in contrast to the single group of boutons of other endings. They displayed a dappled appearance with acetylcholinesterase stain. Dapple endings had morphological features and staining characteristics consistent with motor end plates. Hence, spiralling of nerve fibre endings is shown to be a device for conveying boutons to dapple motor end plates rather than for monitoring the contraction of muscle fibres.