Number Of Optic Nerve Fibers Research Articles

Editorial New Advances in Diagnosis and Management of Glaucoma.

Glaucoma is the first cause of unemendable visual disability and blindness worldwide [1]. If glaucoma is detected at early stages, the visual disability can be prevented or postponed, and consequently its social, economic, and psychic burdens diminished. Although glaucoma is a complex and poorly understood disorder, the primary goal of therapy is lowering Intraocular Pressure (IOP), which is not only one of the most significant risk factors in development of the disease, but also the only modifiable one. Glaucoma is a chronic disease that must be longitudinally assessed and treated based on the appearance of the optic nerve head and evaluation of its function. Traditionally, optic disc evaluation and visual field test along with IOP measurement have been used for glaucoma diagnosis and monitoring. These tests are still of great value in the field of glaucoma, but are subjected to considerable measurement errors, because visual field is a subjective test that requires patient cooperation, and optic disc evaluation is an objective but observer-dependent test. Although visual field testing has been widely used for diagnosis, staging and monitoring the disease, in many patients visual field losses only become detectable after a substantial number of optic nerve fibers has been lost. Therefore, early identification of structural damage to the optic disc and retinal nerve fiber layer is paramount for an early diagnosis of the disease. Heidelberg Retina Tomograph is an objective, observer-independent method for measurement of optic disc parameters, which allows detecting subtle changes in optic nerve head configuration, and hence earlier detection of glaucoma progression [2]. Optical coherence tomography can reliably measure peripapillary retinal nerve fiber layer and macular thickness as an anatomical proxy for visual field test. This test is objective, highly repeatable, and requires less patient cooperation than visual field. Other limitations of visual field such as low vision are also less problematic in these objective tests [3, 4]. However, these devices have their own limitations which should be taken into account while interpreting them. With few exceptions, medical therapy is the first treatment modality in glaucoma patients. Despite a number of pharmacological options, failure of medical treatment is a significant issue owing to drug ineffectiveness and intolerance, but also to poor patient compliance and persistence. Although after introduction of new drugs in mid-1990s, the global number of glaucoma operations has decreased, particularly in the western countries [1], we still need medications with higher potency and fewer side effects. Considering glaucoma as a neurodegenerative disorder, new efforts have been made to prevent or reverse retinal nerve fiber layer loss through neuroprotective or neuroregenerative therapies [5]. Patients with an uncontrolled IOP despite implementing medical and laser therapy need a surgical intervention. For several decades, trabeculectomy and tube shunt have been regarded as milestones of glaucoma surgery. In spite of modifications applied to these procedures to enhance their efficacy and minimize their complications, none of them is perfect and the new glaucoma surgeries do not seem to be a perfect substitution [6]. The pediatric groups of glaucoma patients have their own characteristics and need proper approach in terms of medical and surgical treatment [7]. As the technology advances, and our understanding of glaucoma improves, novel tools and methods are being available for a better diagnosis, monitoring, and treatment of glaucoma. The constellation of review articles that have been gathered in this issue are intended to provide updated information on new advances in different aspects of glaucoma diagnosis and treatment.

Comparative Morphometric Study of the Optic Nerve in One-Humped Camel (Camelus dromedarius) and Donkey (Equus asinus)

Comparative anatomical studies were made measuring several morphological characteristics seen in cross-sections of the optic nerve of one-humped camel (Camelus dromedarius) and donkey (Equus asinus). Six optic nerves from each animal were used in this study. The optic nerve samples were obtained about 5mm behind the eye. The axon numbers and diameters were studied with light and transmission electron microscopes. Axon diameters were measured in samples of 500 axons taken from several locations in a cross section of the optic nerve behind the eye. The total cross-sectional area of the optic nerve was about 35% smaller in the donkey than in the camel. The fibers are organized in fascicles. The fiber density and number was 2.3 times higher in the camel than in the donkey. The total number of optic nerve fibers counted was 1173323 ± 33039 in camels and 495754 ± 10126 in donkeys. The majority of axons were myelinated in the optic nerve of both animals. There was a significant regional variation in the size of optic nerve axons. Large myelinated axons were observed in the dorsal and ventral periphery, whereas smaller myelinated fibers and a high proportion of unmyelinated fibers were found in the center of the nerve.

High-sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina

Small bistratified cells (SBCs) in the primate retina carry a major blue-yellow opponent signal to the brain. Here we show that SBCs also carry signals from rod photoreceptors, with the same sign as S cone input. SBCs exhibited robust responses under low scotopic conditions (<0.01 P*/rod/s). Physiological and anatomical experiments indicated that this rod input arose from the AII amacrine cell mediated rod pathway. Rod and cone signals were both present in SBCs at mesopic light levels. We discuss three implications of these findings. First, more retinal circuits than previously thought may multiplex rod and cone signals, efficiently exploiting the limited number of optic nerve fibers. Second, signals from AII amacrine cells may diverge to most or all of the <20 RGC types in the peripheral primate retina. Third, rod input to SBCs may be the substrate for behavioral biases toward perception of blue at mesopic light levels.

Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging

Previous studies have suggested that retinal ganglion cells and their axons are damaged in patients with Alzheimer disease. The authors performed a case-control study, comparing the optic nerves (clinical examination and scanning laser ophthalmoscopy) of 40 patients with Alzheimer disease and 50 controls. They showed a reduction in the number of optic nerve fibers in patients with Alzheimer disease, with a three-fold greater odds ratio for a larger optic cup-to-disk ratio in patients with Alzheimer disease.—Valérie Biousse

Regeneration of optic nerve fibers following graded injuries in rats

To investigate the changes of retinal ganglion cell (RGC) and their axons, and nerve regeneration ability following graded optic nerve injury (ONI) in rats. A pair of cross-action forceps with 148.0 g clipping pressure was used to clip rat optic nerves for 3, 6, 12, 30 and 60 s to induce graded ONI animal model. The RGC was counted at 0.5, 1, 2, 3 and 7 months and the axons were observed 1, 2 and 3 months post-injury. The regeneration process was observed by transmission electron microscopy. The number of optic nerve fibers in transverse sections was calculated in silver-stained longitudinal sections, and a regeneration index (RI) was calculated based on these numbers. The RI, reflecting the regeneration ability of injured optic nerves, was calculated as follows: (number of nerve fibers 0.5 mm behind injury site-number of nerve fibers 2.5 mm behind injury site)/(number of nerve fibers 0.5 mm retrobulbarly-number of nerve fibers 2.5 mm behind injury site). RGC and axons lost continuously after partial ONI. The loss of RGC was fitted with exponential pattern consisted of two phases, acute losing phase within first two weeks post injury and followed by another phase characterized by slowly reducing of RGC. The loss ratio of RGC increased and the survival ratio decreased with the severity of injury intensity. The loss of RGC and axons was aggregated in severe injury and showed a self-limited trend in mild injury. A large amount of clustered, zonal unmyelinated regeneration fibers were present after injury. The RI was 1.409, 1.490, 0.916, 1.119 and 1.224 following 3, 6, 12, 30 and 60 s clipping injury (chi2 = 281.2, P < 0.01), respectively. Different RI was associated to different injury intensity, with a greater regeneration ability in mild injury. The secondary reaction and regeneration ability vary with graded intensity of optic nerve injury. A self-limited secondary reaction and a more powerful regeneration ability are associated with a mild injury. The repair behavior and the injury may reach a balance and result in a successful regeneration after a certain degree of injury.

Brain Structures of a Medaka Mutant, el(eyeless), in Which Eye Vesicles Do Not Evaginate

Eye development and brain structures of a mutant teleost fish were investigated. The el(eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.

Effect of optic disc size or age on evaluation of optic disc variables

AIMS/BACKGROUNDIt has been reported that the number of optic nerve fibres decrease with age, and the cup/disc (C/D) ratio increases as the optic disc size increases. Consequently, the normal value...

Size and distribution of retinal ganglion cells in the St. Kitts green monkey (Cercopithecus aethiops sabeus).

The topographical distribution of density and the soma size of retinal ganglion cells (RGCs) were studied in the St. Kitts green monkey (Cercopithecus aethiops sabeus). The total number of RGCs, estimated from light microscopic analysis of wholemounted and of transversely sectioned retinae, ranged between 1,183,721 and 1,273,715 (mean 1,228,646). These estimates are comparable to the number of optic nerve fibres (1,220,000) estimated from semithin sections. The topographic distribution of RGCs shows a strong centroperipheral gradient. The soma size distribution of RGCs in Nissl-stained flatmounts falls within a range of between 5.7 microm and 22.9 microm and is comparable to other primate species. Somata of RGCs were found to be generally smaller within the fovea than in peripheral regions. Ganglion cells, as reported for other diurnal primates, are nonuniformly distributed with a slight nasotemporal elongation of isodensity contours, and they exhibit nasotemporal asymmetry in the frequency distribution of soma size. The topography of the RGC distribution of this semiarboreal, ground-dwelling monkey is similar to what has been found in other diurnal Old World species.

Multineuronal codes in retinal signaling.

The visual world is presented to the brain through patterns of action potentials in the population of optic nerve fibers. Single-neuron recordings show that each retinal ganglion cell has a spatially restricted receptive field, a limited integration time, and a characteristic spectral sensitivity. Collectively, these response properties define the visual message conveyed by that neuron's action potentials. Since the size of the optic nerve is strictly constrained, one expects the retina to generate a highly efficient representation of the visual scene. By contrast, the receptive fields of nearby ganglion cells often overlap, suggesting great redundancy among the retinal output signals. Recent multineuron recordings may help resolve this paradox. They reveal concerted firing patterns among ganglion cells, in which small groups of nearby neurons fire synchronously with delays of only a few milliseconds. As there are many more such firing patterns than ganglion cells, such a distributed code might allow the retina to compress a large number of distinct visual messages into a small number of optic nerve fibers. This paper will review the evidence for a distributed coding scheme in the retinal output. The performance limits of such codes are analyzed with simple examples, illustrating that they allow a powerful trade-off between spatial and temporal resolution.

Increased serotonin in the developing superior colliculus does not alter the number or distribution of retinotectal ganglion cells.

Administration of a single subcutaneous dose of 5,7-dihydroxytryptamine (5,7-DHT) to newborn hamsters results in a significant increase in the density of serotoninergic (5-HT) fibers in the superficial layers of the superior colliculus (SC) and marked abnormalities in both the crossed and uncrossed retinotectal projections when these animals reach adulthood (R. Rhoades, C. Bennett-Clarke, R. Lane, M. Leslie, and R. Mooney, 1993, J. Comp. Neurol. 334:397-409). The present study was undertaken to determine whether changes in the retinotectal projection of 5,7-DHT-treated animals were associated with alterations in the number or distribution of retinal ganglion cells in these animals. Nissl staining of retinae from normal adult and 5,7-DHT-treated hamsters revealed no differences between them in the number or average diameter of cells in the retinal ganglion cell layer. Retrograde labeling with horseradish peroxidase (HRP) demonstrated no effect of 5,7-DHT treatment on the number or distribution of ipsilaterally or contralaterally projecting ganglion cells. Neonatal 5,7-DHT administration also had no effect on the distribution of soma diameters for HRP-labeled retinal ganglion cells. Electron microscopic analysis demonstrated no significant difference between the number of optic nerve fibers in the normal and 5,7-DHT-treated hamsters. The results are consistent with the conclusion that the effect of 5,7-DHT on the retinotectal projection may primarily be a function of this toxin, or the increase in 5-HT it induces, on the terminal arbors of retinotectal axons rather than on their parent cells.

A morphological study of the retinal ganglion cells of the Afghan pika ( Ochotona rufescens)

The distribution and morphology of the retinal ganglion cells was studied in a relative of the rabbit, the Afghan pika. The total number of retinal ganglion cells was approximately 170 000. The total number of optic nerve fibers was between 160 000 and 190 000, corresponding to the total number of retinal ganglion cells. Retinal ganglion cells were found to have a horizontal region of high-density. The maximum density was 5250 cells/mm 2. This region was located in the central retina below the optic disc. This area contained numerous closely packed small ganglion cells, while the peripheral retina (especially in the dorsal periphery) contained large ganglion cells more loosely dispersed. The retinal ganglion cells labeled by horseradish peroxidase (HRP) were morphologically classified into three types based on dendritic length and ramification pattern.

Changes in Optic Disk Characteristics and the Number of Nerve Fibers in Experimental Glaucoma

We compared the change in cup/disk ratio and neuroretinal rim area-to-disk area to estimated change in the number of optic nerve fibers in 12 cynomolgus monkeys with unilateral experimental glaucoma. Changes in the cup/disk ratios and neuroretinal rim area-to-disk area were estimated from stereoscopic optic disk photographs that were obtained before and after the development of increased intraocular pressure. Change in the number of optic nerve fibers in the glaucomatous nerves was estimated by comparing them to their fellow normal nerves. A significant linear correlation was present between change in the cup/disk ratios and neuroretinal rim area-to-disk area, and estimated change in the number of optic nerve fibers (r > or = .85; P < .0002). In optic disks with initial cup/disk ratios of 0.2 to 0.3 and neuroretinal rim area-to-disk area of 0.9, an increase in the cup/disk ratio of 0.1 and a decrease of 0.1 in the neuroretinal rim area-to-disk area is associated with a 10% and 9% loss of optic nerve fibers, respectively.

Visual Dysfunction Without Retinitis in Patients With Acquired Immunodeficiency Syndrome

Patients with human immunodeficiency virus infection may have noninfectious and infectious retinopathies, as well as clinical symptoms consistent with optic nerve dysfunction. Noninfectious acquired immunodeficiency syndrome-related retinopathy is seen in most patients with AIDS. Morphologic studies have shown that the number of retrobulbar optic nerve fibers in patients with AIDS is decreased compared to the number of optic nerve fibers in normal control eyes. To determine whether these patients had a visual dysfunction consistent with damage to the macula and optic nerve, 78 subjects (156 eyes) were studied using color-vision and contrast-sensitivity testing. The Farnsworth-Munsell 100-Hue color-vision test was performed on all subjects and age-corrected color-vision scores for all groups were compared. A significant decrease in color discrimination was found in the patients with AIDS (P less than .001). Contrast-sensitivity testing disclosed a deficit of contrast threshold in patients with AIDS at four of five spatial frequencies and in patients with AIDS-related complex at three of the five spatial frequencies examined. This study demonstrated a functional visual deficit in eyes without retinitis consistent with dysfunction of the macula or optic nerve in patients with AIDS.

Quantitative histological study of the optic nerve in species of minnows (Cyprinidae, Teleostei) inhabiting clear and turbid water.

Quantitative analysis of the optic nerve of minnows using light- and electron microscopy demonstrated that anatomical characteristics of the visual system are closely related to habitat turbidity. Species in the genera Notropis and Cyprinella inhabiting predominantly clear water had larger eyes and almost twice as many optic nerve fibers compared to minnows of turbid habitats. No differences were detected in the thickness of myelination, the axon diameter profile, or the number of optic nerve fibers per retinal area, indicating that the relative number of fibers, as well as their anatomical characteristics, are similar in all species and independent of habitat turbidity. It is therefore hypothesized that quantitative differences in the number of visual elements available for sampling and processing in the retina, optic nerve, and optic tectum are sufficient to account for presumed differences in visual performance.

Larger Optic Nerve Heads Have More Nerve Fibers in Normal Monkey Eyes

The cup-to-disc ratio and the neural rim area are used to detect glaucoma damage to the optic nerve. Both parameters are dependent on the size of the optic disc and on the number of optic nerve fibers. We compared the size of the disc in fundus photographs with the number of nerve fibers in 25 normal monkey eyes. The number of fibers increased linearly with an increasing disc area. One must know the size of the optic disc to evaluate properly the cup-to-disc ratio or neural rim area.

Optic nerve hypoplasia in children.

Optic nerve hypoplasia (ONH) is characterised by a diminished number of optic nerve fibres in the optic nerve(s) and until recently was thought to be rare. It may be associated with a wide range of other congenital abnormalities. Its pathology, clinical features, and the conditions associated with it are reviewed. Neuroendocrine disorders should be actively sought in any infant or child with bilateral ONH. Early recognition of the disorder may in some cases be life saving.

Substance P-immunoreactivity in the developing human retinogeniculate pathway

Substance P has been immunohistochemically localized in the human optic nerves and lateral geniculate nuclei during the prenatal period from 13-14 to 37 weeks of gestation. Substance P-immunoreactive fibres were present in the optic nerves and lateral geniculate nuclei in all these ages thereby providing direct evidence of this undecapeptide being associated with the retinogeniculate pathway. At 16-17 weeks, greater numbers of fibres were observed than in the later ages. It is likely that the reduction in number of optic nerve fibres seen quantitatively during prenatal life may partly be due to the loss of substance P fibres.

Chronic Human Glaucoma Causing Selectively Greater Loss of Large Optic Nerve Fibers

Eighteen eyes of 12 persons with chronically elevated intraocular pressure (IOP) were studied histologically to determine the number and diameter of optic nerve fibers. In some eyes, automated perimetry had been performed. Optic nerve fibers larger than the mean diameter were killed more rapidly than smaller fibers, although no fiber size was completely spared at any stage of atrophy. The number of optic nerve fibers varies considerably among normal eyes. The authors confirmed that the death of a substantial proportion of optic nerve fibers precedes detectable visual field loss.

Taurine depletion leads to loss of rat optic nerve axons

The number of axons in the optic nerve have been examined in rat pups raised by control or taurine-depleted mothers, at 21, 28 and 40 days after birth. Optic nerves from the mother rats were also studied. Taurine depletion of dams and some litters after weaning was achieved by in vivo treatment with guanidinoethyl sulfonate, an inhibitor of taurine transport. Retinal taurine content was reduced by this procedure and reductions in axon density (axons per area) were found in some groups. Comparison of axon densities obtained from light or electron micrographs suggested that taurine-deficient pups might have a higher proportion of small diameter fibres than controls, perhaps due to slowed growth and/or myelination. Reductions in the calculated total number of optic nerve fibres attained statistical significance consistently only in the treated dams. Ganglion cell degeneration may be direct or secondary to effects on taurine-sensitive elements at more distal retinal sites.

Changes in the numbers of optic nerve fibers during late prenatal and postnatal development in the albino rat

We have estimated from electron micrographs the numbers of axons in the optic nerves of a series of albino rats at 8 different ages ranging from embryonic day (E)18 through postnatal day 28. The number of axons was found to reach a maximum of about 325,000 (324,790 ± 38,589) on E20, and to decline to about 275,000 (273,744 ± 20,973) by the day of birth. By the middle of the second postnatal week, the number was further reduced to a stable figure of just over 100,000 (105,809 ± 7,610). This represents a loss of two-thirds of the axons from the peak value at E20, and suggests that there is a comparable degree of cell death among the retinal ganglion cells. The reduction in the number of optic nerve fibers is not affected significantly by the removal of the opposite eye at birth.