Quantitative studies of the optic nerve fiber layer in the chicken retina.

The optic nerve fiber layer (NFL) of the chicken retina was studied quantitatively and morphologically at 17 positions along seven radially arranged bands from the dorsal tip of the pecten oculi using electron microscopy. The number of nerve fibers was counted in areas 6 microm in width x the full thickness of the NFL. Myelinated nerve fibers in the NFL were also identified immunohistochemically using anti-myelin basic protein serum. The dorsal area (dorsal, dorso-temporal and dorso-nasal bands) in the retina had thin NFL and contained the largest number of nerve fibers, which were mainly thin and unmyelinated. The ventral area (ventral and ventro-temporal bands) had a thick NFL and contained a relatively small number of nerve fibers, many of which were myelinated. The nasal band had the thickest NFL and contained as many nerve fibers as the dorsal area, with the temporal band showing a high ratio of myelinated fibers. The band had a thick NFL and contained many nerve fibers with a relatively low ratio of myelinated fibers. The relationship between the number and composition of nerve fibers in the NFL to the chicken visual characteristics was discussed. Although the myelin in the chicken retina was loose type, the myelin-forming cells were similar in appearance to dense oligodendrocytes. retina, morphometry, myelinated fiber, nerve fiber layer.     

Comparative optic nerve physiology: implications for glaucoma, neuroprotection, and neuroregeneration

The axoplasm of optic nerve axons moves bidirectionally at various speeds along an intra-axonal pressure gradient from the retinal ganglion cell (RGC) somata toward its synapse, and from the synapse towards the RGC somata. The axoplasmic flow of optic nerve axons is precarious even at normal intraocular pressures (IOP) as it moves from the intraocular optic nerve through the scleral lamina cribrosa to the intraorbital optic nerve. The scleral lamina cribrosa is not simply a porous region of the sclera but a specialized extracellular matrix of the central nervous system whose movement during fluctuations in IOP can affect optic nerve axoplasmic flow. The abundant optic nerve blood supply maintains adequate optic nerve head perfusion through a process of vascular autoregulation. Glaucoma is associated with reduced optic nerve axoplasmic flow and compromised optic nerve circulation such that RGC death due to glutamate excitotoxicity and neurotrophin deprivation result.     

Morphologic changes in the lamina cribrosa of beagles with primary open-angle glaucoma

Optic nerve axoplasmic flow is known to be impaired at the scleral lamina cribrosa in Beagles with hereditary primary open-angle glaucoma and is similar to the condition in human beings. Trypsin and detergent digestion to remove all neural, vascular, and glial cellular tissue revealed a well-developed scleral lamina cribrosa in the normal dog in this study. Beagles with primary open-angle glaucoma had signs of mechanical distortion of the anterior lamina cribrosa prior to the detection of ophthalmoscopic changes in the optic nerve head. This change in the supporting architecture of the optic nerve began early and increased in severity as the disease process progressed.     

Immunohistochemistry of the extracellular matrix of the normal equine lamina cribrosa

Purpose To use immunohistochemical techniques to identify and localize the structural macromolecules of the extracellular matrix (ECM) of the normal adult equine lamina cribrosa in order to make comparisons to the extracellular matrix of the lamina cribrosa of horses with glaucoma. METHODS: Normal eyes of five adult horses between 5 and 10 years of age were fixed in 10% neutral buffered formalin and embedded in paraffin. Polyclonal rabbit-derived antibodies against human elastin, laminin, fibrillin-1, and collagen types I, III and IV, and polyclonal goat-derived antibodies against collagen type VI were used as primary antibodies. Transverse and longitudinal histologic sections of the optic nerve head and lamina cribrosa were stained using several dilutions of the primary antibodies, biotinylated link antibody, horseradish peroxidase-labeled streptavidin, and 3,3'-diaminobenzidine as a chromogen. The immunohistochemical staining patterns were qualitatively interpreted. RESULTS: The normal adult horse lamina cribrosa labeled positively for collagen types I, III and VI, laminin, elastin and fibrillin. Collagen type VI staining of the laminar ECM was most intense, followed by labeling for collagen types III and I, respectively. Laminar blood vessels were weakly positive for laminin and slightly positive for type IV collagen. The scleral ECM of the laminar insertion zone had more intense labeling for collagen types I and VI than did the laminar plates. CONCLUSIONS: The extracellular matrix of the laminar plates of the adult equine lamina cribrosa is similar to the dog as it consists of elastic and collagen fibers (with collagen types VI, III and I). Both the normal dog and horse lamina display more intense staining of collagen type VI than is found in the ECM of the normal human lamina cribrosa. The macromolecular structure of the equine lamina cribrosa suggests that it is a very resilient structure that may provide some protection to the optic nerve axons during episodes of elevated intraocular pressure.     

Porencephaly with an optic organ abnormality in a beagle dog

A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral hemisphere and an adhesion area between the cerebral cortex and the skull, which was partially thickened. Additionally, the right optic nerve showed a slight decrease in diameter. Histopathological examination revealed increased glial fibers and collagen fibers, hemosiderin deposition, and an increased number of microglia in the adhesion area, along with a marked reduction of the cerebral parenchyma. In the right eyeball, the retina and optic nerve showed focal atrophy in the nerve fiber layer and inner granular layer to full retinal atrophy and hypoplasia of the myelinated nerve fibers, respectively. Electron microscopic examination revealed hypoplasia of the myelin sheath of nerve fibers in the right optic nerve. This is an extremely rare case of porencephaly and congenital optic nerve hypoplasia, along with independent retinal thinning.     

Retinal vascular patterns in domestic animals

In this paper a morphological study of the retinal vascular patterns in various species of domestic animals is reported. A classification of these patterns into four well-defined groups is described. In the domestic ruminants, pigs and carnivores the retina contains a compact plexus of blood vessels located in the major part of the light-sensitive portion of the retina (euangiotic or holangiotic pattern). In other domestic animals blood vessels are present only in a smaller part of the retina. In the rabbit, vessels are confined to a broad horizontal band coincident with the area of dispersion of the myelinated nerve fibres. The larger of these vessels are readily visible macroscopically (merangiotic pattern). In the horse and the guinea pig the retinal blood vessels are minute and restricted to the direct neighbourhood of the optic disc (paurangiotic pattern). The avian retina is completely avascular (anangiotic pattern), but a densely vascularised pecten oculi is attached to the linear optic nerve head and protrudes far into the inferior part of the vitreous body.     

Structural and ultrastructural study of the intracranial portion of the oculomotor, trochlear and abducent nerves in dog

The right intracranial portion of the oculomotor, trochlear and abducent nerves were removed from six adult German shepherd dogs and analysed by light and electron microscopy. In all cases the nerve sectional area was calculated. Unmyelinated and myelinated fibres were analysed and number, diameter and cross-sectional area were calculated. In myelinated fibres, also calculated were the corresponding axon area and diameter, and myelin sheath thickness. The mean number of myelinated fibres was 8543.50 +/- 1231.85 being the unmyelinated 1402 +/- 241.58 in the oculomotor nerve; 1509 +/- 223.17 and 287.67 +/- 72.28 in the trochlear nerve and 2473.00 +/- 211.41 and 231.25 +/- 92.67 respectively in the abducent. The mean diameter was 10.23 +/- 0.68 microm in myelinated and 0.43 +/- 0.21 for unmyelinated in oculomotor nerve, 10.53 +/- 0.55 microm and 0.33 +/- 0.04 for the trochlear, and 10.45 +/- 1.27 microm and 0.47 +/- 0.09 in the abducent nerve respectively. This study reveals that oculomotor, trochlear and abducent nerves of the dog show structural and ultra-structural features similar to the same nerves in other species.     

Ultrastructural changes in laminar optic nerve capillaries of beagles with primary open-angle glaucoma

Ultrastructural examination of optic nerve capillaries in the canine lamina cribrosa revealed many spherical, membrane-bound, electron-dense inclusions that closely resembled Weibel-Palade bodies, in pericytes and endothelial cells of preglaucomatous, early, moderately, and advanced affected Beagles with hereditary primary open-angle glaucoma. This ultrastructural difference between the laminar capillary endothelial cells of normal and glaucomatous Beagles could represent a functional vascular disorder, because Weibel-Palade bodies are associated with microcirculatory abnormalities.     

Conduction velocities and myelinated fiber diameter spectra of the infraorbital and palpebral nerves of the dog

Maximum conduction velocities of compound-action potentials of the infraorbital (ION) and palpebral (PN) nerves were determined by averaging potentials evoked and recorded through subcutaneous needle electrodes. The specificity of the stimulating and recording sites was verified by recording before and after cutting the nerves. Conduction times for orthodromically and antidromically conducted potentials of the ION were essentially the same. The unipolarly recorded antidromic compound-action potentials of the ION were of higher peak-to-peak amplitude and were more reliably recorded than were the bipolarly recorded orthodromic action potentials. Areas of cutaneous innervation were not found for the PN. Neuromuscular blockade eliminated the volume-conducted muscle action potentials that were recorded after PN stimulation, allowing triphasic nerve action potentials to be recorded unobscured. Mean conduction velocities were: ION = 83.9 +/- 3.5 m/s; PN = 56.4 +/- 2.8 m/s. Distributions of the external diameters of myelinated fibers within the ION and the PN were determined.     

Morphometric Comparison between Controlateral Sciatic Nerves in the Male and Female Rabbit

Some morphometrical parameters of the axons making up the controlateral sciatic nerves, both in the male and female rabbits were calculated and compared by means of a Zeiss Vidas image analyser (Ober Kochen, Germany). The results show that the fibres constituting the left nerve have a greater mean diameter but a lower mean density than those constituting the right nerve. This suggests that the diameter of the myelinated fibres and the density of both the myelinated and unmyelinated fibres do not vary from male to female. On the other hand, the G ratio and the diameter of the unmyelinated axons do, since the nerves on the right side (in both sexes) have higher morphometric values, on average, than the controlateral ones.     

A sensory neuropathy affecting Long-haired Dachshund dogs

A sensory neuropathy affecting three Long-haired Dachshunds is described. The clinical signs were similar and include disturbances of proprioception, pain sensation and urinary function. Sensory nerve conduction was absent in one dog. Nerve biopsy showed a severe depletion of myelinated fibres in sensory nerves and widespread unmyelinated fibre pathology. Clinical and pathological evidence suggests that this axonal neuropathy, which is possibly of inherited origin, affects both myelinated and unmyelinated fibres in sensory and autonomic nerve trunks.     

Unilateral optic nerve hypoplasia and hydrocephalus in a Pekingese

A 3-year-old, castrated male Pekingese was examined 2 days after automobile-induced trauma. Multiple pelvic injuries and visual deficits in the right eye were identified. During a subsequent postmortem examination, multiple pelvic fractures were confirmed; however, there was no evidence of head injury. Both globes were bilaterally symmetrical and grossly normal. The intraorbital and intracranial portions of the right optic nerve were threadlike and rudimentary in appearance, while the left optic nerve was grossly normal. Moderate dilatation of the left lateral ventricle was noted. Microscopically the right optic nerve and left nerve tract contained few identifiable nerve fibers. The right optic disc was depressed, and there was thinning of the optic nerve fiber and ganglion cell layers of the retina. No microscopic abnormalities were evident in the left optic nerve, optic disc, retina and right optic tract. The histologic changes in the right eye are consistent with optic nerve hypoplasia. The relationship between the optic nerve/optic tract lesions and the hydrocephalus is unknown.     

Comparative retinal ganglion cell and optic nerve morphology

The optic nerve is divided in four regions: intraocular, intraorbital, intracanalicular, and intracranial. The vertebrate retinal ganglion cells are classified by morphology, physiology and soma size. Species differences and similarities occur with retinal ganglion cells. Alpha retinal ganglion cells have large somata, large dendritic fields, large-diameter axons, and are most dense in the peripheral retina. Beta retinal ganglion cells have smaller diameter somata, smaller dendritic fields, small diameter axons, and predominate in the central retina. Gamma retinal ganglion cells are a heterogenous class of cells and have small diameter axons, and slow axon conduction velocities. The spatial distribution and organization of the retinal ganglion cells extends retinotopically through the nerve fiber layer, optic nerve, optic chiasm, optic tract, lateral geniculate nucleus, and visual cortex. The retinal nerve fiber layer thickness decreases from the optic disk toward the periphery of the retina. The retrobulbar optic nerve axon counts and axon density vary by species, with larger nerves having higher axon counts. Decussation of the optic nerve axons at the optic chiasm varies with 100% decussation in most birds and fish, 65% in cats, 75% in dogs, 80–90% in large animals, and 50% in primates. Centrifugal axons also occur in the optic nerve and may represent a method by which the brain can influence retinal activity.     

Tongue atrophy as a neurological finding in hereditary polyneuropathy in Alaskan malamutes

BackgroundTongue atrophy with wrinkling as a clinical sign of inherited polyneuropathies has not been reported in dogs.ObjectivesClinically describe tongue atrophy as well as morphology of the tongue and hypoglossal nerve in Alaskan malamute polyneuropathy (AMPN).AnimalsSix client‐owned Alaskan malamute dogs diagnosed with AMPN, all homozygous for the causative mutation in the N‐myc downstream‐regulated gene 1 (NDRG1) and 1 neurologically normal control Alaskan malamute.MethodsProspective case study. Clinical and neurological examinations were performed on affected dogs. Necropsy samples from the tongue muscle and hypoglossal nerve were examined by light and electron microscopy.ResultsAll affected dogs had abnormal wrinkles and grooves on the dorsal surface of the tongue, a clinical sign not described previously in dogs with AMPN. Electromyography of the tongue performed in 2 dogs showed spontaneous activity. Five affected dogs underwent necropsy studies. Histopathology of the tongue showed groups of angular atrophic myofibers and changes in the hypoglossal nerve included thinly myelinated fibers, small onion bulbs, folded myelin, and axonal degeneration.Conclusion and Clinical ImportanceHistopathologic changes in the tongue and hypoglossal nerve were consistent with previously reported changes in skeletal muscle and other nerves from dogs with AMPN. Therefore, we conclude that macroscopic tongue atrophy is part of the disease phenotype of AMPN and should be considered a potential clinical sign in dogs with polyneuropathies.     

Heritability of multifocal retinal dysplasia in American Cocker Spaniels

Multifocal retinal dysplasia was detected in 96 American Cocker Spaniels. Affected dogs were part of approximately 500 American Cocker Spaniels examined from 1972 to 1976 in statewide survey clinics for inherited cataracts and progressive retinal atrophy. The dysplastic retina was observable ophthalmoscopically in dogs as young as 3 to 4 weeks and as old as 7 years. Ophthalmoscopic features varied, depending on whether the dysplastic foci were in the tapetal or non-tapetal portion of the fundus. Over the tapetum, dysplastic foci appeared as multiple small irregularities of diminished and altered tapetal reflectivity. In the non-tapetal fundus, dysplasia appeared as areas of decreased pigmentation. Blindness or other apparent visual deficits were not observed in affected dogs. Histologic examination of affected eyes revealed focal dysplasia limited to the retina and optic nerve. Abnormalities included localized areas of retinal folding, rosettes, and retinal pigment epithelium hypertrophy and hyperplasia. Pedigree analysis demonstrated that 71 of the 96 affected dogs were related and could be identified in an extended pedigree. A recessive mode of inheritance was suggested, because in 5 litters (born to 10 affected parents), all 23 progeny that lived were affected. A dominant or polygenic mode of inheritance could not be ruled out.     

Morphologic and morphometric study of the facial nerve in clinically normal adult dogs.

A morphologic and morphometric study was carried out on the facial nerve: to determine normal histologic data in myelinated fibers of clinically normal young adult dogs; to establish reference values for mean fiber diameter, and to delineate the relative diameter frequency distribution curve. Few degenerative changes were observed in single teased-nerve fibers and semithin cross-sectional nerve preparations. Statistical difference was not observed between left and right facial nerves. The distribution of fiber diameters in the facial nerve was unimodal. Mean (+/- SD) fiber diameter of the facial nerve was 3.92 +/- 1.18 microns. Approximately 89% of fibers in the facial nerve had diameter between 3 and 6 microns. Fiber diameter ranged from 2 to 12 microns; however, less than 1% of fibers had diameter greater than 8 microns.     

Histomorphometry of the porcine scleral lamina cribrosa surface

The lamina cribrosa surface of the pig was examined using trypsin digestion, scanning electron microscopy, and computerized image analysis. Six normal eyes from healthy pigs were studied. The total intralaminar scan area, total number of laminar pores, median individual laminar pore areas, median individual pore form factors, and mean pore density were determined for the dorsal, ventral, nasal and temporal hemicircles, the dorsal-nasal, dorsal-temporal, ventral-nasal, and ventral-temporal quadrants, and their central and peripheral subdivisions. The mean (+/- SD) total intralaminar scan area was 8.29 +/- 1.54 mm2. The mean (+/- SD) total laminar pore count was 517 +/- 73 pores. The mean pore count was significantly larger in the ventral than the dorsal hemicircle (292 +/- 39 vs. 225 +/- 38 pores, respectively; P = 0.001), and significantly greater in the periphery compared to the center (388 +/- 58 vs. 129 +/- 27 pores, respectively; P = 0.0001). The overall mean (+/- SD) pore density was 67 +/- 7 pores mm-2. Mean pore density was significantly greater in the ventral than the dorsal hemicircle (70 +/- 8 vs. 64 +/- 6 pores mm-2, respectively; P = 0.019), and significantly greater in the center compared to the periphery (75 +/- 9 vs. 60 +/- 8 pores mm-2, respectively; P = 0.020). The mean (+/- SD) median individual pore area was 3752 +/- 572 &mgr;m2. The mean (+/- SD) median pore form factor was 0.680 +/- 0.035. No significant regional differences were found in mean median pore form factor or mean median individual pore areas. The intralaminar optic nerve of pigs is 55.1% non-neural connective and vascular tissue. A pigmented ventral fascial groove in the scleral lamina cribrosa appears unique to the porcine lamina cribrosa, and may be a vestige of the embryonic optic fissure.     

Squamous cell carcinoma causing blindness and ophthalmoplegia in a cat

Ophthalmoplegia and blindness caused by squamous cell carcinoma were reported in a cat. Unilateral functional deficits of cranial nerves II, III, IV, and VI and of the sympathetic nerve supply caused blindness, complete ophthalmoplegia, and Horner syndrome. Radiography and computed tomography revealed a proliferating bony lesion associated with the right tympanic bulla, right temporal bone, right side of the mandible, and left frontal bone. A focal area of bony destruction involved the right sphenoid bone. The cat was euthanatized and necropsied. Squamous cell carcinoma was identified invading the bones and rostral part of the right side of the skull. The tumor had extended through the sphenoid bones into the region of the cavernous sinus and had surrounded the cranial nerves passing through this region. It also had invested connective tissue surrounding the optic nerves and had invaded the right globe through the lamina cribrosa. This represents an unusual distribution for ocular cranial squamous cell carcinoma in a cat.     

Rapid diagnosis of retina and optic nerve abnormalities in canine patients with and without cataracts using chromatic pupil light reflex testing

Objective To develop fast and reliable testing routines for diagnosing retina and optic nerve diseases in canine cataract patients based on chromatic properties of the pupillary light reflex response. Procedures Seventy‐seven canine patients with a history of cataract and decreased vision (43 patients with cataracts and no evidence of retina or optic nerve disease, 21 patients with cataracts and retinal degeneration [RD], 13 patients with cataracts and retinal detachment [RDT]), 11 canine patients with optic neuritis (ON) and 23 healthy dogs were examined using chromatic pupillary light reflex (cPLR) analysis with red and blue light and electroretinography. Results Electroretinography analysis showed statistically significant deficits in a‐ and b‐wave amplitudes in dogs with cataracts and RD, or cataracts and RDT, when compared to dogs with cataracts without evidence of retinal abnormalities. Evaluation of b‐wave amplitudes showed that presence of 78.5‐μV (or lower) amplitudes had high sensitivity of 100% (95% CI: 87.2–100%) and high specificity of 96.7% (95% CI: 88.4–100%) in RD and RDT. Evaluation of cPLR responses using red light showed that presence of the pupil end constriction diameter of 5.5 mm (or higher) had moderately high sensitivity of 76.5% (95% CI: 50.1–93.2%) and high specificity of 100% (95% CI: 91.2–100%) in detecting RD and RDT. Optic neuritis patients had absent cPLR responses, regardless of the visual status. Conclusions and Clinical Relevance Chromatic evaluation of the pupillary light reflex is a rapid and accurate test for diagnosing retina and optic nerve diseases in canine patients.