Distinctive histopathologic features of canine optic nerve hypoplasia and aplasia: a retrospective review of 13 cases

Canine optic nerve hypoplasia (ONH) and aplasia (ONA) are significant neuro-ophthalmologic disorders that have been reported in several species. The purpose of this study was to describe the distinctive histopathologic features of ONH and ONA in canine patients identified from a collection of 20 000 ocular submissions at the comparative ocular pathology laboratory of Wisconsin from 1989 to 2006. The following information about ONH and ONA cases was collected: signalment, and clinical and gross findings, including unilateral vs. bilateral involvement. Microscopic evaluation was performed, with attention to optic nerve malformation, retinal ganglion cell (RGC) and nerve fiber layer (NFL) loss, and retinal disorganization. The distribution of retinal vasculature was recorded and a search for unusual findings of ONH and ONA was performed. Information and histologic documentation was available for 13 cases. Eight cases of ONH and five cases of ONA were identified. The average group age was 20.2 months and 16.1 months, respectively. The most common breed was the Shih Tzu (3/13). ONH usually presented bilaterally (7/8); all ONA cases presented as a unilateral disease (5/5). The morphologic findings in the optic nerve (ON) in ONH included variable degrees of ON hypoplasia and gliosis, as well as ectopic vestigial ON remnants within orbital nerves and connective tissues. The NFL was detected in the majority of the ONH cases; however, RGCs were rare or absent. Mild retinal disorganization was seen occasionally. Most cases of ONH were associated with regional peripheral retinal blood vessel extension into the vitreous, leaving the peripheral retina avascular. In ONA cases the retinal blood vessels, NFL and RGCs were totally absent and retinal disorganization was severe. Distinctive microscopic features encountered in ONA included anterior segment dysgenesis in some cases. The retina in these cases was stretched across the posterior lens capsule, never making contact with the posterior pole of the globe. The current study reviews the human and veterinary literature pertaining to ONH and ONA, compares ONH and ONA in dogs, and presents related ophthalmic histopathologic findings that have not been reported previously.     

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.     

Microvasculature of the hamster eye: scanning electron microscopy of vascular corrosion casts

The architecture of the retina, choroid and anterior eye segment was investigated in 12 Syrian hamsters using scanning electron micrographs of methylmethacrylate corrosion casts. The hamster eye receives its primary blood supply from the long posterior ciliary artery, which directly enters the optic nerve head, and divides into three branches: the central retinal artery and medial and lateral long posterior ciliary arteries. In the retina the central retinal artery divides into six radiating branches. Retinal arterioles form a slender and long course to capillaries. Retinal capillaries are extremely thin in diameter and form a sparse capillary network. The choroid is supplied by the long posterior ciliary arteries. Choroidal arterioles exhibit a thick and short course to the choriocapillaris. The choriocapillaris is thick and sinusoid-like, forming a dense network in the choroid. The ciliary body, iris and bulbar conjunctiva are supplied by the anterior ciliary arteries, which are branches of the long posterior ciliary arteries. Capillaries supplying the anterior margin of the ciliary process are large in diameter with an irregular bore, forming a thoroughfare channel draining blood in the ciliary arterioles into the pars plana vessels. Blood from the retina is drained by the central retinal veins. Venules from the anterior eye segment empty into the vortex veins via the pars plana vessels. Venous blood from the choroid is drained only by vortex veins via the choroidal veins. The functional significance of the vascular architecture and species differences are discussed.     

Fine structure of the retino-optic nerve junction in dogs

In most mammals, the optic nerve fibers are myelinated in its extraocular part (EON) but not in its intraocular part (ION) and also in the retina. Transitional zone from the myelinated to unmyelinated optic nerve usually lies in the central part to the lamina cribrosa. It has been known that dogs contain exceptionally myelinated fibers in ION by light microscopy. The aim of this study was to investigate electron microscopically the retino-optic nerve junction in dogs and re-evaluate the barrier to migration of oligodendroblasts into ION. Fourteen adult dogs were used. EON was largely myelinated. In ION the percentage of myelinated fibers decreased gradually toward the retina. A narrow area of ION adjoining the retina was completely unmyelinated. In most mammalian optic nerves, oligodendrocytes are not found in ION. It has been suggested that oligodendroblasts are prevented from migrating from EON into ION; that is to say, there is a barrier to migration of oligodendroblasts. The lamina cribrosa, a dense meshwork of fibrous astrocytic processes, and a defect in the blood optic nerve barrier have been proposed as a candidate for the barrier to migration. Our results suggest, however, that these factors, at least in dogs, would be not involved in the formation of a barrier to migration of oligodendroblasts.     

Study of the distribution of retinal blood vessels in buffaloes (Bos bubalis)

The distribution of retinal blood vessels in the eye of buffalo was studied macroscopically and microscopically in twenty-two eyes of healthy animals. After macroscopic observation, 12 of 22 eyes were used for histological study. Ten eyes were stained with hematoxylin and eosin and two eyes with PAS stain. The present findings revealed that the eye of the buffalo was characterized by the complex network of retinal blood vessels (holangiotic or euangiotic). The central retinal artery and vein pierced the eye through the optic disc and gave off several branches. There were four pairs of primary vessels that were named dorsal, ventral, nasal and temporal retinal arteries and veins. The veins anastmosed with each other at the optic disc to form a somewhat circle. Three patterns of the distribution of blood vessels were described. The distribution of the arteries and veins was the same.     

Blindness in a wild American black bear cub (Ursus americanus)

An approximately six‐month‐old wild American black bear (Ursus americanus) was found wandering in Saskatchewan and was presented to the Veterinary Medical Centre of the Western College of Veterinary Medicine for apparent blindness. Clinical examination confirmed an inability to navigate a photopic maze, bilateral tapetal hyper‐reflectivity, fundi devoid of retinal vessels, and small pale optic nerve papillae. Single‐flash electroretinography revealed A and B‐wave amplitudes of approximately 40 and 140 microvolts, respectively, in both eyes. Histologic abnormalities included bilateral optic papillary mineralization and bilateral segmental optic nerve degeneration, with occasional intralesional lymphocytes confirmed with immunohistochemistry for CD3+. There was also bilateral multifocal retinal dysplasia, gliosis, lymphocytic retinitis, a complete lack of retinal blood vessels, an intravitreal vascular membrane, and a mild lymphocytic–plasmacytic uveitis with small pre‐iridal cellular membranes. The presence of a positive ERG in a blind bear with numerous retinal ganglion cells and degenerative changes in the optic nerve are most consistent with vision loss due to optic nerve injury, which given the young age of the bear likely occurred during ocular development. The presence of ocular inflammation suggests this injury resulted from an inflammatory/infectious process. The etiology could not be determined. Hepatic concentrations of vitamin A were within the normal reference range for domestic species. Pan‐herpesvirus PCR and immunohistochemistry for canine distemper virus and Toxoplasma gondii were negative, although this does not rule out these or other infectious etiologies. This represents the first case report of neonatal or congenital ocular abnormalities in an ursid species.     

Normal structure and age-related changes of the equine retina

Investigations of the pathophysiology of ocular diseases require a detailed knowledge of the microanatomy of the eye. The available information is still inadequate for the equine retina despite the importance of eye diseases in equine medicine. Here we provide a comprehensive analysis of the histologic features of the horse eye as a reference for future studies. Thirty normal eyes of 15 healthy horses were examined immediately after slaughter. The retina of the horse differs considerably in the degree and quantity of neurons and glial elements as well as in vascular patterns compared to the retina of other domestic animals. Morphometric analysis revealed that the thickness of the retina varies between 80 microm at the ora serrata and 250 microm medial to the optic disc. Approximately 90% of the equine retina is comparatively thin (< 130 microm). This is a physiologic response to the distance that oxygen can diffuse in avascular retina. Ganglion cells form a single layer in all parts of the retina. The majority of ganglion cells are very large Nissl-positive cells. Small Nissl-negative ganglion cells are less abundant. A high ganglion cell density is found only in the central area. Vascularization is virtually absent from the retina with the exception of a narrow strip around the disc of the optic nerve, as revealed by lectin histochemistry. Light microscopy of the eyes of older horses repeatedly revealed cystoid degenerations in the retina adjacent to the pars plana of the ciliary body, as well as a destruction of the regular layering of the peripheral region of the retina.     

Macroanatomic,light and scanning electron microscopic structure of the pecten oculi in northern bald ibis (Geronticus eremita)

Eyes are the most primarily required sensory organs during the migration of migratory birds and Northern Bald Ibises (Geronticus eremita) are known to make long migrations. This study examined for the first time the structure of pecten oculi in northern bald ibises by using macroscopic anatomy as well as light and electron microscopic methods. In the study 20 eye globes from 10 adult bald ibises were used. The pecten was of pleated type. As in most bird species, it was located on the optic nerve head and projects into the vitreous from the optic nerve head. The wider basal part was observed to attached to retina and its free apical part was found in camera vitrea bulbi embedded in corpus vitreum. The pecten had 13–14 accordion like pleats lying between the basal and apical parts. In addition to arterial and venous vessels, numerous capillary vessels as well as melanocytes were observed within each pleat. The bridge binding the pleats at the apical part showed a stronger pigmentation compared to other parts of the pecten. The results of the study indicated that the general morphology of pecten oculi in northern bald ibises which is a migratory bird species were similar to that in other diurnal bird species.     

Comparative Doppler imaging of the ophthalmic vasculature in normal Beagles and Beagles with inherited primary open-angle glaucoma

The objective of this study was to compare orbital and ocular vasculature velocity, measured by Doppler imaging, in normal Beagles and Beagles with inherited primary open-angle glaucoma. Eight normal Beagles and 13 Beagles with different stages of primary open-angle glaucoma were evaluated twice with a 2–4-week period between measurements. Doppler imaging was performed with the dogs anesthetized, and the Doppler transducer applied directly on the corneal surface. The majority of the orbital vasculature (external ethmoidal artery; internal ophthalmic artery and vein; and external ophthalmic artery and vein) and ocular blood vessels (anterior ciliary artery and veins; long posterior ciliary arteries; short posterior ciliary arteries; primary retinal arteries; and the vortex veins) were identified and Doppler blood velocity parameters were determined. The glaucomatous dogs demonstrated significant differences in the Doppler velocity parameters of several orbital vessels (external ethmoidal, external ophthalmic, and internal ophthalmic arteries), and several ocular vessels (anterior ciliary, short posterior ciliary, and long posterior ciliary arteries). These differences included decreased blood velocities, and increased pulsatility and resistive indexes. The Doppler blood flow velocities of the primary retinal arteries were unchanged between the normal and glaucomatous dogs. In the glaucomatous dogs, the Doppler imaging suggests increased vascular resistance downstream in both the orbital and ocular vasculature. These blood velocity parameter changes may be primary or secondary, and may offer therapeutic opportunities to increase perfusion, prolong the retina and optic nerve head function, and maintain vision in the canine glaucomas.     

Spontaneous buphthalmos in the Djungarian hamster (Phodopus sungorus campbelli)

Four Djungarian hamsters ( Phodopus sungorus campbelli ) were examined because of insidious globe enlargement, visual impairment and secondary altered behavior. Buphthalmos, deep anterior chambers, widely dilated pupils and poor to absent pupillary light reflexes were evident bilaterally in all four animals. Pale retinae and atrophic optic nerve heads were observed in the oldest hamsters. Light microscopic findings, including uveal atrophy, retinal atrophy (especially the inner retina), and a relative decrease in ganglion cells and optic nerve atrophy, were consistent with glaucoma. The etiology was unclear, but a genetic predisposition cannot be excluded.     

Ocular anomalies and holoprosencephaly in a lamb

The brain and eyes from a 1-day-old, male mixed-breed lamb with bilateral microphthalmia were examined. Bilateral ventral colobomata of choroid, sclera, retina and optic nerve were accompanied by agenesis of the optic nerve, and dilated lateral and third ventricular cavities that communicated with the subarachnoid space. Abundant neuroretinal tissue extending through the colobomatous defect to retro-orbital connective tissue, the meningeal surface and ventricular system were identified by histologic examination. Positive immunolabeling of these structures for recoverin (a photoreceptor marker) established the retinal origin of ectopic structures. The optic nerve was replaced by a short fibrous stalk containing glial nests. Sections of brainstem revealed extensive architectural disorganization. A developmental abnormality resulting from defective optic nerve and retina compartmentalization, accompanied by abnormalities of midline development consistent with the holoprosencephaly syndrome, was diagnosed. These lesions are consistent with signaling defects in the sonic hedgehog signaling pathway. Genetic and toxic causes of sonic hedgehog signaling defects are discussed.     

Cytologic appearance of retinal cells included in a fine‐needle aspirate of a meningioma around the optic nerve of a dog

A 6‐year‐old Wirehair Dachshund had a meningioma around the optic nerve that caused exophthalmos. A benign mesenchymal tumor was suspected based on the cytologic pattern of a fine‐needle aspirate, and a meningioma was diagnosed by histopathologic examination. In addition to the meningioma cells, the cytologic smears included groups of cells from apparently 4 layers of normal retina. In particular, uniform rod‐shaped structures in the cytologic sample could suggest rod‐shaped bacteria, but these structures were identified as cylindrical outer segments of photoreceptor rod cells. Other retinal structures recognized included pigmented epithelial layer cells with their uniquely formed pigment granules, the characteristic bi‐lobed, cleaved nuclei from the outer nuclear layer, and nerve tissue likely from the outer plexiform layer of the retina.     

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.     

Vascular changes associated with chorioretinal and optic nerve colobomas in rats (Crj: CD(SD), IGS)

OBJECTIVE: Three female adult rats (Crj: CD(SD) IGS) with colobomatous anomalies were investigated. MATERIALS AND METHODS: The microvascular changes of the coloboma were studied using the techniques of fluorescein angiography, histology and scanning electron microscopy (SEM) of vascular corrosion casts. RESULTS: Fluorescein angiography revealed the pits of the optic disk as a dark hole with some abnormalities in vessel arrangement. Light microscopy confirmed the presence of attenuated lamina cribrosa, retinal dysplasia and marked dilation of the retinal veins. SEM revealed that the optic disk coloboma formed a crater-like pit and that central retinal vessels ran a tortuous course along the bottom and side of the crater. Capillaries in the optic nerve head were missing in the affected area. The central retinal veins were thick and had various changes such as strangulation, rough surface structures, mural voids and evaginations, which represent loss of integrity of the vascular wall. CONCLUSIONS: These vascular changes that are associated with colobomatous anomalies may impede the retinal circulation and be responsible for the fluctuating fluorescein pattern during fluorangiogram of affected animals. The lesions of the vascular wall may increase the subretinal fluid due to the leakage of fluid, thus causing the maculopathy or serous retinopathy, which is frequently associated with posterior pole coloboma.     

Scanning electron microscopy of corrosion casts of the optic nerve microcirculation in dogs

Scanning electron microscopy of vascular corrosion casts of the optic nerve region in normal and glaucomatous Beagles demonstrated that the blood supply to the laminar optic nerve is derived from short posterior ciliary arteries, cilioretinal arteries, and longitudinal pial vessels. The short posterior ciliary arteries formed a ring of striated pillars around the scleral canal. The central retinal artery was not present in the dog. Differences between the casts in normal and glaucomatous dogs were not detected.     

Retinal and optic nerve diseases.

Basic knowledge of the normal appearance and variations of the equine fundus coupled with frequent practice in ophthalmology will allow equine practitioners to be confident when assessing the equine fundus during ophthalmic examinations. Once the normal variations are mastered, appreciation of retinal, choroidal, optic nerve, and vitreal abnormalities is possible. Congenital and acquired lesions of the equine retina, optic nerve, and vitreous are discussed and illustrated.     

Light and electron microscopic studies on the pecten oculi showing blood–retina barrier properties in Turkey’s native Gerze chicken

The pecten oculi is a highly vascularized and pigmented organ that projects from the optic disc into the vitreous body in the avian eye. In this study, the pecten oculi of Turkey's native Gerze chicken was examined by light and scanning electron microscopy. Furthermore, the localization of some adherens junction components (E-cadherin and pan-cadherin) in intact vessels of the blood–retina barrier was investigated by immunohistochemistry. In the Gerze chicken, the pecten oculi was a thin structure, which was located over the head of the discus nervi optici and projected from the retina into the corpus vitreum. The pecten oculi consisted of 18–21 highly vascularized pleats, joined apically by a bridge and resembled an accordion in appearance. Hyalocytes and melanocytes were observed around the small and large vessels. The morphometric data of the pecten oculi showed that there were no statistical differences in terms of sex. The immunohistochemical analysis of the pecten oculi, which is used as a model for the investigation of the formation and maturation of the barrier properties in the central nervous system, revealed cytoplasmic E-cadherin and pan-cadherin immunoreactivity in the endothelial cells of the small, large and capillary vessels. These observations suggest that while the morphological and histological structure of the Gerze chicken's pecten oculi was generally similar to that of other diurnal domestic birds, the pecten oculi, a model system for vascular differentiation and the blood–retina barrier, expressed different cadherins.     

Characterization of structure and function of the mouse retina using pattern electroretinography, pupil light reflex, and optical coherence tomography

Objective To perform in vivo analysis of retinal functional and structural parameters in healthy mouse eyes. Animal Studied Adult C57BL/6 male mice (n?=?37). Procedures Retinal function was evaluated using pattern electroretinography (pERG) and the chromatic pupil light reflex (cPLR). Structural properties of the retina and nerve fiber layer (NFL) were evaluated using spectral-domain optical coherence tomography (SD-OCT). Results The average pERG amplitudes were found to be 11.2?±?0.7?μV (P50-N95, mean?±?SEM), with an implicit time for P50-N95 interval of 90.4?±?5.4?ms. Total retinal thickness was 229.5?±?1.7?μm (mean?±?SEM) in the area centralis region. The thickness of the retinal nerve fiber layer (mean?±?SEM) using a circular peripapillary retinal scan centered on the optic nerve was 46.7?±?0.9?μm (temporal), 46.1?±?0.9?μm (superior), 45.8?±?0.9?μm (nasal), and 48.4?±?1?μm (inferior). The baseline pupil diameter was 2.1?±?0.05?mm in darkness, and 1.1?±?0.05 and 0.56?±?0.03?mm after stimulation with red (630?nm, luminance 200?kcd/m(2) ) or blue (480?nm, luminance 200?kcd/m(2) ) light illumination, respectively. Conclusions Pattern electroretinography, cPLR and SD-OCT analysis are reproducible techniques, which can provide important information about retinal and optic nerve function and structure in mice.     

Fine Structure of the Bovine Tapetum Fibrosum

The fine structure of the tapetum lucidum of the domestic cow was studied by electron microscopy. In this ungulate the reflective layer is a tapetum fibrosum situated in the choroid and mainly restricted to the superior fundus. The tapetum is composed of a large array of fine extracellular collagen fibrils separated into lamellae by fibrocytes. The collagen fibrils display the normal cross-striations of native collagen, are 0.2 μm in diameter and are arranged in a hexagonal pattern with a center-to-center spacing of about 0.2 μm. The diameter and spacing of these fibrils is consistent with the constructive interference of reflected light. A vascular lamella adjacent to the retinal epithelial layer contains the choriocapillaris and some irregularly arranged collagen fibrils. The tapetum is pierced by blood vessels which supply the choriocapillaris. Over the tapetum the retinal epithelium is non-pigmented while in nontapetal regions this layer is pigmented. The choriocapillaris is not indented into the retinal epithelium as is the case in species with a tapetum cellulosum.     

Angiostatin and integrin alphavbeta3 in the feline, bovine, canine, equine, porcine and murine retina and cornea

PURPOSE: Angiogenesis is tightly controlled in the ocular tissues of domestic animals but its mechanisms are not fully understood. This is largely because of insufficient data on the expression of molecules that impact angiogenesis. Because angiostatin and one of its receptors integrin alphavbeta3 inhibit and promote angiogenesis, respectively, we hypothesized that the normal retina and cornea of domestic animals would express angiostatin but not integrin alphavbeta3. PROCEDURE: Normal eyes of the cat, cow, dog, horse, pig and rat were evaluated for angiostatin and integrin alphavbeta3 by light and electron immunocytochemistry and estern blots. RESULTS: Angiostatin was detected in the corneal epithelium of the cat, dog, horse, pig and rat, but was not found in cow corneal epithelium. Angiostatin was localized in the nerve fiber layer, ganglion cell layer, inner and outer plexiform layers, and the photoreceptor layer of the cat, cow, dog and rat. Horse and pig retinas showed additional staining in the matrix of the inner nuclear layer. Immunogold electron microscopy further confirmed angiostatin in cat retina. Western blots showed angiostatin in corneal and retinal homogenates. Integrin alphavbeta3 was absent in cornea and retina of all the species studied. CONCLUSION: These data show that angiostatin, an inhibitor of angiogenesis, is present while integrin alphavbeta3, which promotes angiogenesis, is absent in normal cornea and retina of the domestic animals in this study with the exception being angiostatin absence in cow corneal epithelium. Therefore, angiostatin may contribute to the anti-angiogenic environment in the normal domestic animal eye while its absence in the cow may contribute to greater propensity for corneal vascularization. Because integrin alphavbeta3 is one of the receptors for angiostatin, its absence may prevent angiostatin from killing normal retinal and corneal cells.