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.     

Anterior segment dysmorphogenesis of the eye and glaucoma in MG-W gerbils

Unilaterally swollen eyes were histopathologically characterized in four MG-W gerbils. The primary lesions resided in the anterior segment of the eye where neural crest cells play a critical role in embryonic development. They included indistinct filtration angle, unformed canal of Schlemm, hypoplastic iris, and ciliary body. The findings noted in the retina, optic nerve, optic tract, and lateral geniculate nucleus were consistent with the lesions induced following the persistent elevation of intraocular pressure as a result of insufficient drainage of aqueous humor. Thus, the present cases observed in the eyes of MG-W gerbils exemplified the anterior segment dysmorphogenesis associated with inadequate neural crest migration or differentiation, leading to subsequent glaucoma.     

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.     

Unilateral degeneration of retina and optic nerve in Fischer-344 rats

Unilateral degeneration of the retina and optic nerve was observed among Fischer-344 (F-344) rats fed a semi-purified synthetic feed. Further studies were conducted using standard cereal-based and synthetic diets. Beginning at 4 weeks of age, all experimental rats (169 F-344 rats) were fed various diets and were examined for morphologic and functional changes in the retina and optic nerve. No ocular lesions were observed in any F-344 rats prior to 21 weeks of age, whether fed a synthetic diet or a standard diet; however, approximately 16% (13/86) of the F-344 rats examined between 57 and 64 weeks of age developed unilateral degeneration of the retina and optic nerve. On the other hand, the F-344 rats fed the synthetic diet developed the degenerative lesions by 30 weeks of age, while the F-344 rats fed the standard diet did not develop lesions over this shorter time period. Degenerative changes of the affected retinas and optic nerves were closely related with functional abnormalities evaluated by electroretinogram and visual evoked potentials. In contrast with the F-344 rats, Long-Evans rats that were fed either the synthetic or standard diet up to the age of 68 weeks (77 rats) did not develop the ocular lesions. There was no apparent relationship of the development of the lesions with dietary modification, toxicity or trauma; thus, these observations appear to indicate that spontaneous unilateral degeneration of the retina and optic nerve occurs in F-344 rats and that these ocular lesions may be accelerated by the feeding of certain semi-purified synthetic diets.     

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.     

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.     

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.     

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.     

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.     

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.     

Ophthalmomyiasis (interna posterior) of the posterior segment and central nervous system myiasis: Cuterebra spp. in a cat

A unilateral ophthalmomyiasis posterior in a 5-year-old female spayed Domestic Long-haired cat of a third or fourth stage instar Cuterebra spp. larvae is reported. The cat was presented for depression and anorexia. The organism was found on physical examination at presentation. The cat was euthanized because of the worsening systemic condition. The larva was demonstrated by histopathology with coagulation necrosis and hemorrhage of the optic nerve, retina and choroid, and anterior uveitis. No significant cerebrum and anterior brain stem lesions were found.     

The pathology of blindness in new-born calves caused by hypovitaminosis A

Blindness attributed to vitamin A deficiency afflicted 47 out of 197, and 15 out of 29 new-born dairy calves on 2 farms. Other clinical signs included doming of the forehead, thickening of the carpal joints, incoordination and weakness. Gross lesions in 8 of the calves examined consisted in hydrocephalus and thickened occipital and sphenoid bones. In 4 of these calves the optic nerves were constricted as a result of a reduction in size and dorsoventral narrowing of the optic canals. Microscopical changes in the optic nerves were characterized by necrosis, demyelination and fibrosis. Oedema or gliosis of the optic disc occurred in some of the calves. Retinal lesions included atrophy and gliosis of the ganglion cell layer and the nerve fibre layer. Three of the calves showed focal retinal dysplasia with occasional rosette formation.     

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.     

Spectral domain optical coherence tomography (SD-OCT) assessment of the healthy female canine retina and optic nerve

Objective To provide normative data for canine whole retinal thickness (WRT), nerve fiber layer thickness (NFL), photoreceptor layer thickness (PR), and outer nuclear layer thickness (ONL) using spectral domain optical coherence tomography. Animal studied: Twelve healthy adult intact female beagles. Procedure Horizontal volume scans through the area dorso‐temporal from the optic nerve (superior retina), and the area ventro‐temporal from the optic nerve (inferior retina) were used to evaluate the thickness of retinal NFL, PR, ONL, and WRT. Peripapillary circular scans were used to evaluate NFL thickness. Statistical analyses were performed to compare the thickness of the individual layers between the superior and inferior retina (paired t‐test). One‐way analysis of variance (ANOVA) was used to compare the thickness of peripapillary NFL between the superior, inferior, temporal and nasal quadrants of the circle scan. Results The WRT, PR, and NFL thickness were greater in the superior than in the inferior retina (198.7 ± 9.6 μm vs. 164.4 ± 6.4 μm, P < 0.0001; 95.5 ± 6.5 μm vs. 78.8 ± 7.4 μm, P < 0.0001; and 26.4 ± 1.6 μm vs. 25.0 ± 1.9 μm, P = 0.0236, respectively). No statistical difference was found between the ONL thickness of the superior and inferior retina (50.1 ± 6.4 μm vs. 44.3 ± 3.6, P = 0.0578). Peripapillary NFL thickness showed a similar tendency as the linear scans, with the superior quadrant having the greatest thickness (91.26 ± 7.0 μm) and the inferior quadrant being the thinnest (76.42 ± 9.2 μm) (P < 0.001). Conclusions Results of our in vivo studies showed significant differences between thickness values for the superior (tapetal) and inferior (nontapetal) retinal regions.     

萱草根素对家兔中枢神经损害的病理学研究

本研究旨在对萱草根素中毒家兔中枢神经系统进行病理学研究。从北黄花菜根中提取萱草根素，用1％的淀粉溶液配制成2％混悬液，试验组家兔每只每天灌服萱草根素混悬液4mL／kg，对照组灌服等量的1％淀粉溶液。于处理后第4、7、10、13、16、19天进行常规病理学检查。试验第4天大脑、小脑、脊髓和视神经中的神经纤维出现脱髓鞘变化，在小脑从白质中央向两侧进行性扩展，在脊髓从边缘向中央扩展，最终呈丝瓜络样变；第7天起，蒲肯野氏细胞和脊髓神经细胞发生固缩、坏死；第10天，大脑神经细胞出现坏死、凋亡，并且数目逐渐增多，出现噬神经现象，视网膜萎缩，节细胞固缩、溶解消失。超微结构观察显示，髓鞘变薄，板层崩解、断裂、分离，失去原来的致密结构；神经细胞染色体边集，线粒体肿胀、消失并空泡化、粗面内质网扩张，结构模糊。结果表明，萱草根素可引起神经纤维脱髓鞘和神经细胞的广泛性坏死，并最终导致家兔失明和死亡。     

Canine ocular gliomas: a retrospective study

Objective The purpose of this paper is to classify glial tumors observed in the canine retina and optic nerve, describe the histopathological features and provide prognostic information on these neoplasms. Methods The database of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) was searched to collect canine glioma cases. Clinical and follow-up information was gathered from submission forms and an extensive follow-up survey. Slides were reviewed to describe the histopathological characteristics of the neoplasm and classify them. Immunohistochemistry for Glial Fibrillary Acidic Protein (GFAP) was performed in all cases. Results 18 canine glioma cases were found in the COPLOW database. There was no breed or gender predilection. The mean age was 9.33 ± 3.67 years. Follow-up information was available for 12 dogs, 8 of which were dead at the time of most recent contact, with a survival time ranging from 0 days (globes received after euthanasia) up to 20 months post-enucleation. In 6 of the 8 dogs that had died during this stud), tumor extended to the margin where the optic nerve had been sectioned. Light microscopic examination of the optic nerve of the affected eyes of four dogs that were still alive during this study revealed no tumor at this surgical margin. One neoplasm was classified as low-grade astrocytoma, 5 tumors as medium-grade astrocytoma, 11 tumors as high grade-astrocytoma and 1 tumor as oligodendroglioma. GFAP was positive in all but two tumors. Conclusion Retinal and optic nerve gliomas may be considered as differential diagnoses of intraocular and orbital masses. The metastatic potential appears to be low, but ascending invasion into the ventral aspect of the brain is possible.     

Choroidal melanomas in dogs

The clinical and morphological features of intraocular melanocytic masses that originated in the choroid of five dogs were compared. Two of the cases had been reported previously and the authors have examined the pathological material. Histologically, the choroidal melanocytic tumors had several features in common and appeared to be entities distinct from melanocytic tumors of the anterior uveal tract or the epibulbar region. The tumors were well-delineated with tapered edges. They occurred in the posterior quadrant and two tumors had infiltrated the optic nerve. The tumors contained plump, strap-like polyhedral cells, with minimal nuclear anaplasia and no mitotic figures. The retina overlying the tumor mass was detached, and the retinal pigment epithelium in this area was swollen and contained intracytoplasmic autofluorescent lipopigment. In two cases, the basement membrane of the retinal epithelium was disrupted by the tumor and pigmented cells infiltrated into the retina, the subretinal space, and the posterior chamber. In one case, retinal detachment was complete and accompanied by intraocular hemorrhage. Melanocytic tumors of the canine choroid have features in common with choroidal nevus and melanocytoma in human eyes.     

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.     

Optic pathway degeneration in Japanese black cattle

Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.