Prelaminar Region Research Articles

Effects of Stress and Strain on the Optic Nerve Head on the Progression of Glaucoma.

In primary open-angle glaucoma, the rate of retinal nerve fiber layer thickness decrease was negatively correlated with lamina cribrosa strain, which was associated with intraocular pressure and optic nerve head geometric factors. We hypothesized that the biomechanical deformation of the optic nerve head (ONH) contributes to the progression of primary open-angle glaucoma (POAG). This study investigated the biomechanical stress and strain on the ONH in patients with POAG using computer simulations based on finite element analysis (FEA) and analyzed its association with disease progression. We conducted a retrospective analysis that included patients diagnosed with early-to-moderate stage POAG. The strains and stresses on the retinal nerve fiber layer (RNFL) surface, prelaminar region, and lamina cribrosa (LC) were calculated using computer simulations based on FEA. The correlations between the rate of RNFL thickness decrease and biomechanical stress and strain were investigated in both the progression and non-progression groups. The study included 71 and 47 patients in the progression and non-progression groups, respectively. In the progression group, the factors exhibiting negative correlations with the RNFL thickness decrease rate included the maximum and mean strain on the LC. In multivariate analysis, the mean strain on the LC was associated with optic disc radius, optic cup deepening, axial length, and mean intraocular pressure (IOP), whereas the maximum strain was only associated with mean IOP. In early-to-moderate stage POAG, the rate of RNFL thickness decrease was influenced by both the mean and maximum strain on the LC. Strains on the LC were associated with mean IOP, optic disc radius, axial length, and optic cup deepening. These results suggest that not only IOP but also ONH geometric factors are important in the progression of glaucoma.

Transcriptional profiling of retinal astrocytes identifies a specific marker and points to functional specialization.

Astrocyte heterogeneity is an increasingly prominent research topic, and studies in the brain have demonstrated substantial variation in astrocyte form and function, both between and within regions. In contrast, retinal astrocytes are not well understood and remain incompletely characterized. Along with optic nerve astrocytes, they are responsible for supporting retinal ganglion cell axons and an improved understanding of their role is required. We have used a combination of microdissection and Ribotag immunoprecipitation to isolate ribosome-associated mRNA from retinal astrocytes and investigate their transcriptome, which we also compared to astrocyte populations in the optic nerve. Astrocytes from these regions are transcriptionally distinct, and we identified retina-specific astrocyte genes and pathways. Moreover, although they share much of the "classical" gene expression patterns of astrocytes, we uncovered unexpected variation, including in genes related to core astrocyte functions. We additionally identified the transcription factor Pax8 as a highly specific marker of retinal astrocytes and demonstrated that these astrocytes populate not only the retinal surface, but also the prelaminar region at the optic nerve head. These findings are likely to contribute to a revised understanding of the role of astrocytes in the retina.

A numerical investigation of passive acoustic mapping for monitoring bubble-mediated focused ultrasound treatment of the spinal cord.

Focused ultrasound (FUS) combined with intravenous microbubbles (MBs) has been shown to increase drug delivery to the spinal cord in animal models. Eventual clinical translation of such a technique in the sensitive spinal cord requires robust treatment monitoring to ensure efficacy, localization, safety, and provide key intraprocedural feedback. Here, the use of passive acoustic mapping (PAM) of MB emissions with a spine-specific detector array in the context of transvertebral FUS sonications is investigated in silico. Using computed tomography-derived human vertebral geometry, transvertebral detection of MBs is evaluated over varying source locations with and without phase and amplitude corrections (PACs). The impact of prefocal cavitation is studied by simulating concurrent cavitation events in the canal and pre-laminar region. Spatially sensitive application of phase and amplitude is used to balance signal strengths emanating from different axial depths in combination with multiple dynamic ranges to elicit multisource viewing. Collectively, the results of this study encourage the use of PAM in transvertebral FUS applications with PACs to not only localize sources originating in the spinal canal but also multiple sources of innate amplitude mismatches when corrective methods are applied.

Optic Disc Edema in Astronauts from a Choroidal Point of View.

INTRODUCTION: Optic disc edema has been well documented in astronauts both during and after long-duration spaceflight and is hypothesized to largely result from increased pressure within the orbital subarachnoid space brought about by a generalized rise in intracranial pressure or from sequestration of cerebrospinal fluid within the orbital subarachnoid space with locally elevated optic nerve sheath pressure. In addition, a recent prospective study documented substantial spaceflight-associated peripapillary choroidal thickening, which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. In the present article, based on the above, we offer a new perspective on the pathogenesis of microgravity-induced optic disc edema from a choroidal point of view. We propose that prolonged microgravity exposure may result in the transudation of fluid from the choroidal vasculature, which, in turn, may reach the optic nerve head, and ultimately may lead to fluid stasis within the prelaminar region secondary to impaired ocular glymphatic outflow. If confirmed, this viewpoint would shed new light on the development of optic disc edema in astronauts.Wostyn P, Gibson CR, Mader TH. Optic disc edema in astronauts from a choroidal point of view. Aerosp Med Hum Perform. 2022; 93(4):396-398.

Microstructure and resident cell-types of the feline optic nerve head resemble that of humans

The lamina cribrosa (LC) region of the optic nerve head (ONH) is considered a primary site for glaucomatous damage. In humans, biology of this region reflects complex interactions between retinal ganglion cell (RGC) axons and other resident ONH cell-types including astrocytes, lamina cribrosa cells, microglia and oligodendrocytes, as well as ONH microvasculature and collagenous LC beams. However, species differences in the microanatomy of this region could profoundly impact efforts to model glaucoma pathobiology in a research setting. In this study, we characterized resident cell-types, ECM composition and ultrastructure in relation to microanatomy of the ONH in adult domestic cats (Felis catus). Longitudinal and transverse cryosections of ONH tissues were immunolabeled with astrocyte, microglia/macrophage, oligodendrocyte, LC cell and vascular endothelial cell markers. Collagen fiber structure of the LC was visualized by second harmonic generation (SHG) with multiphoton microscopy. Fibrous astrocytes form glial fibrillary acidic protein (GFAP)-positive glial columns in the pre-laminar region, and cover the collagenous plates of the LC region in lamellae oriented perpendicular to the axons. GFAP-negative and alpha-smooth muscle actin-positive LC cells were identified in the feline ONH. IBA-1 positive immune cells and von Willebrand factor-positive blood vessel endothelial cells are also identifiable throughout the feline ONH. As in humans, myelination commences with a population of oligodendrocytes in the retro-laminar region of the feline ONH. Transmission electron microscopy confirmed the presence of capillaries and LC cells that extend thin processes in the core of the collagenous LC beams. In conclusion, the feline ONH closely recapitulates the complexity of the ONH of humans and non-human primates, with diverse ONH cell-types and a robust collagenous LC, within the beams of which, LC cells and capillaries reside. Thus, studies in a feline inherited glaucoma model have the potential to play a key role in enhancing our understanding of ONH cellular and molecular processes in glaucomatous optic neuropathy.

Quantitative analysis of astrocyte and axonal density relationships: Glia to neuron ratio in the optic nerve laminar regions

Astrocytes are critical for the maintenance of retinal ganglion cell (RGC) axonal function and viability, and form a key component of the functional neurovascular unit. Recently, we described the quantitative properties of astrocytes in relation to the capillary distributions in optic nerve laminar regions. Here, we provide a quantitative analysis of astrocytes and RGC axons in longitudinal sections of optic nerve tissue. Histological and immunocytochemical techniques are used to demonstrate the density of astrocytes, RGC axons and glia-neuron ratios across the pre laminar, lamina cribrosa and post laminar compartments of the optic nerve head (ONH). A study of human, pig, horse and rat optic nerves was performed and comparisons are made between species. This study demonstrates that the distribution of astrocytes correlates closely with the density of axonal processes, in accordance with the functional requirement of different regions of the ganglion cell axon. There was a consistency of glia-neuron ratios in the majority of laminar compartments, except for the human and rat prelaminar regions, which demonstrated lower ratios of astrocyte to axonal processes. The distribution of astrocytes may reflect a functional susceptibility to development of disease in the prelaminar region of the optic nerve. Interspecies comparison at the lamina cribrosa showed strikingly consistent glia-neuron ratios. Collectively, our findings suggest there may be a critical ratio of glia to neuron needed to maintain healthy cellular physiology across different laminar compartments of the optic nerve, with particular importance for the health of the lamina cribrosa region. It is possible that, in disease processes, the glia-neuron relationships across the different laminar compartments may be perturbed and this may be relevant for the development of glaucoma. Emerging technologies may further aid our understanding in how the physiology of optic nerve tissue cellular structure may be affected by changes to ONH characteristics and elevated intraocular pressure induced damage. Such findings may also permit the early identification of RGC axonal injury by identifying quantifiable changes in structural tissue architecture when pathophysiological pathways predominate.

A finite element study of posterior eye biomechanics: The influence of intraocular and cerebrospinal pressure on the optic nerve head, peripapillary region, subarachnoid space and meninges

Abstract Several biomechanical factors have been associated with the development of glaucoma. However, although optic nerve head (ONH) biomechanics have been previously analysed, other ocular zones have been less explored. Therefore, in this study, the effect of intraocular and cerebrospinal fluid pressure (CSFP) on the ONH, peripapillary region (PPR), optic nerve subarachnoid space (SAS) and meninges have been investigated. Two finite element models of the eye were made from one anatomical configuration, including the complete PPR (choroid, retina, and sclera), all meningeal layers and the SAS. Each of the models were subjected to 12 different eye pressures, and one model was additionally subjected to 20 cerebrospinal pressures. Furthermore, the biomechanical impact of each meningeal layer and SAS on the ONH and PPR was assessed. Global results indicated that the greatest strains occurred in the retina, followed by the prelaminar region and lamina cribrosa (LC). With an increase in intraocular pressure (IOP), all of the PPR showed thinning; nevertheless, the retina was the layer most affected. Additionally, the results showed that the postlaminar tissue was the region most deformed by CSFP variations. Despite this, a low CSFP, associated with ocular hypertension, caused an increase in retinal, choroidal and LC strains, and posterior displacement of central and medial regions of the LC and prelaminar tissue, as well as a change in postlaminar tissue biomechanics. Finally, the meninges produced an important reduction in ONH strains due to IOP fluctuations, and variations in SAS stiffness had a strong influence on strains within the ONH and PPR.

Dilated Prelaminar Paravascular Spaces as a Possible Mechanism for Optic Disc Edema in Astronauts.

INTRODUCTION: A number of ophthalmic abnormalities, including optic disc edema, have been reported in several astronauts involved in long-duration spaceflights. An increased understanding of factors contributing to this syndrome, initially designated visual impairment and intracranial pressure syndrome and recently renamed spaceflight-associated neuro-ocular syndrome, has become a high priority for ESA and NASA, especially in view of future long-duration missions, including trips to Mars. The underlying pathophysiological mechanisms of this syndrome are still not well understood. In the present paper, we propose that optic disc edema in astronauts may occur, at least in part, as a result of retention of interstitial fluid in distended paravascular spaces at the prelaminar region of the optic nerve head. Preflight, in-flight, and postflight analysis of the optic nerve head and surrounding structures by optical coherence tomography in long-duration International Space Station crewmembers could provide important structural information in this respect.Wostyn P, De Winne F, Stern C, De Deyn PP. Dilated prelaminar paravascular spaces as a possible mechanism for optic disc edema in astronauts. Aerosp Med Hum Perform. 2018; 89(12):1089-1091.

Evaluation of Prelaminar Region and Lamina Cribrosa with Enhanced Depth Imaging Optical Coherence Tomography in Pseudoexfoliation Glaucoma.

Objectives:To analyze optic nerve head images of pseudoexfoliative glaucoma (PXG) patients and healthy volunteers obtained with enhanced depth imaging spectral domain-optical coherence tomography (SD-OCT).Materials and Methods:Seventy patients with PXG and 68 age- and gender-matched healthy subjects were included in this prospective study. The prelaminar tissue and lamina cribrosa were imaged using spectralis OCT with the enhanced depth imaging technique. PXG disease stage was determined with visual field to evaluate relationships between prelaminar tissue thickness (PTT), lamina cribrosa thickness (LT) and disease severity.Results:There was no significant difference between the PXG group and control group with regard to age, gender, central corneal thickness, or axial length. The mean PTT (93.1±44.5 μm, p<0.05) and LT (206.3±33.6 μm p<0.05) values of the PXG group were significantly lower compared to the control group in enhanced depth imaging OCT measurements. The PXG patients were divided into stages according to visual field defect severity. While a significant difference was not detected in PTT based on disease stage (p>0.05), a statistically significant difference was detected between stages for LT (p<0.05).Conclusion:A thinner PTT was correlated with the presence of PXG but not with the severity of glaucoma. In addition, LT has a stronger relationship with disease severity and progression compared to PTT.

Microvascular Density Is Associated With Retinal Ganglion Cell Axonal Volume in the Laminar Compartments of the Human Optic Nerve Head.

To quantify associations between microvascular density and retinal ganglion cell (RGC) axonal volume in the laminar compartments of the human optic nerve head (ONH). Eleven normal human ONHs were evaluated. Antibodies were used to label the vascular endothelium (factor VIII-related antigen/von Willebrand factor antibody) and RGC axons (neurofilament heavy antibody). Three-dimensional analysis of confocal scanning laser microscope images was used to study microvascular density and RGC axonal volume in the prelaminar, anterior lamina cribrosa, posterior lamina cribrosa, and retrolaminar compartments. Microvascular volume was significantly different between laminar compartments (P < 0.0083) and was greatest in the prelaminar region, occupying 11.7% of tissue volume. Microvascular volume per RGC axonal volume and cumulative capillary length per RGC axonal volume were significantly different between laminar compartments (all P < 0.0083). Both were significantly greater in the posterior laminar cribrosa (27.4% and 2.28 × 10-3 μm/μm3, respectively). Microvascular density is closely coupled to RGC axonal volume in the ONH. The posterior laminar cribrosa is a site of high blood supply as evidenced by a greater ratio of microvascular density to RGC axonal volume. The greater percentage of tissue volume occupied by microvasculature in the prelaminar region may implicate it as a site where significant connections between the central retinal artery and short posterior ciliary arteries occur.

Three-dimensional Optical Coherence Tomography Imaging and Treatment of Glaucomatous Optic Nerve Head Defects Associated with Schisis-like Maculopathy

We present the three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) findings of schisis-like maculopathy associated with structural changes of the optic nerve (ON) head as well as the treatment outcomes of a case of advanced glaucoma. In addition to ophthalmological examination, B-scan and 3D-SD-OCT images of the ON head, peripapillary retina, and the macula were obtained. The B-scan images only detected typical retinoschisis findings. However, the 3D-SD-OCT images of the ON head revealed defects of various sizes, shapes, and depths at the outer wall of the prelaminar and laminar regions of the ON canal. The 3D images were able to establish that these defects were both adjacent to and interconnected with the retinal layers. The patient successfully received 3D-SD-OCT-guided thermal laser treatment that is used in congenital optic disc pits complicated with macular schisis. In brief, 3D-SD-OCT is very useful for demonstrating the ON head defects that can lead to schisis-like maculopathy in cases of advanced glaucoma.

Optic nerve head and intraocular pressure in the guinea pig eye

The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I–V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were qualitatively similar in structure in pigmented and albino guinea pigs. The well-organized, collagen-based LC of the guinea pig ONH is similar to that described for tree shrews and more similar to the human LC than that of other rodents that lack collagen. Based on these latter structural similarities the guinea pig would seem a promising model for investigating the relationship between myopia and glaucoma.

Pathogenesis of optic disc edema in raised intracranial pressure.

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure.

Is There Any Role for the Choroid in Glaucoma?

The choroid is part of the uveal tract and is a heavily vascularized bed that also contains connective tissue and melanin pigment. Given the role of the choroidal vasculature in the blood supply of the anterior laminar and prelaminar regions of the optic nerve head, the peripapillary choroid might be a relevant target for investigation in patients with glaucoma. The purpose of this paper is to critically review the current understanding of potential role of the choroid in the pathogenesis of glaucomatous damage.

Expression of glucose transporters in the prelaminar region of the optic-nerve head of the pig as determined by immunolabeling and tissue culture.

BackgroundTo develop the use of cultured tissue of the prelaminar optic nerve of the pig to explore possible alterations of the astrocyte-axon metabolic pathways in glaucoma, we map the distribution of the glucose transporters GLUT1 and GLUT3 in fresh and cultured tissue.MethodsWe monitor cell survival in cultures of the prelaminar optic-nerve tissue, measuring necrosis and apoptosis markers biochemically as well as morphologically, and establish the presence of the glucose transporters GLUT1 and GLUT3. We map the distribution of these transporters with immunolabeling in histological sections of the optic nerve using confocal and electronic transmission microscopy.ResultsWe find that the main death type in prelaminar culture is apoptosis. Caspase 7 staining reveals an increment in apoptosis from day 1 to day 4 and a reduction from day 4 to day 8. Western blotting for GLUT1 shows stability with increased culture time. CLSM micrographs locate GLUT1 in the columnar astrocytes and in the area of axonal bundles. Anti-GLUT3 predominantly labels axonal bundles. TEM immunolabeling with colloidal gold displays a very specific distribution of GLUT-1 in the membranes of vascular endothelial cells and in periaxonal astrocyte expansions. The GLUT-3 isoform is observed with TEM only in axons in the axonal bundles.ConclusionsTissue culture is suitable for apoptosis-induction experiments. The results suggest that glucose is transported to the axonal cleft intracytoplasmically and delivered to the cleft by GLUT1 transporters. As monocarboxylate transporters have been reported in the prelaminar region of the optic-nerve head, this area is likely to use both lactate and glucose as energy sources.

High spatial resolution imaging mass spectrometry of human optic nerve lipids and proteins.

The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

Cupping of the optic disk after methanol poisoning.

To assess the frequency and significance of optic disk cupping after methanol poisoning. We retrospectively reviewed the medical records of 50 consecutive patients with methanol poisoning, including visual acuity, pupillary reaction, and optic disk features such as the presence and degree of cupping. All patients were examined in the chronic phase after optic nerve damage. Optic disk cupping ≥0.8 c/d was present in at least one eye of 22 of these 50 patients (43/100 eyes). Severity of cupping was statistically symmetric in the two eyes, and increasing severity of cupping was correlated with worse visual acuity (p=0.007) and increasing visual field loss. Degree of cupping was significantly correlated with increasing patient age but not with putaminal necrosis. Optic disk cupping after methanol poisoning may be more common than previously recognised. Cupping in this setting may reflect toxicity of methanol metabolites to axons and glial cells in the prelaminar, laminar and retrolaminar regions, and seems to be important as a marker for worse optic nerve damage.

Chemoarchitecture of glial fibrillary acidic protein (GFAP) and glutamine synthetase in the optic nerve of the monkey (&lt;i&gt;Macaca fuscata&lt;/i&gt;): An immunohistochemical study

An immunohistochemical analysis of the chemoarchitecture of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) was conducted in the monkey optic nerve. The optic nerve has been divided into 3 regions: the prelaminar, lamina cribrosa, and retrolaminar regions. However, it currently remains unclear whether the chemoarchitecture of GFAP and GS is homogeneously organized, especially in the retrolaminar region. Strong-to-moderate GFAP immunoreactivity was observed in all 3 regions. The retrolaminar region was further divided into anterior (RLa) and posterior (RLp) retrolaminar regions. More GFAP immunoreactive punctations were observed in the RLa region than in the RLp region. Regarding GS immunoreactivity, moderately GS immunoreactive glial cells were observed in the prelaminar and retrolaminar regions. In the retrolaminar region, there were more of these cells in the RLa region than in the RLp region. GS immunoreactivity was markedly weaker in the prelaminar and retrolaminar regions than in the retina. Thus, the chemoarchitecture of GFAP and GS was heterogeneously organized in the retrolaminar region, and the RLa region was the main GS distribution site in the retrolaminar region. Since GS is a key enzyme of glutamate metabolism, these results may provide clues as to how glutamate is metabolized in the primate optic nerve.

Morphological and morphometric changes in rat optic nerve microvessels in a glaucoma experimental model

AimTo study the morphological and morphometric changes produced in the capillaries of the optic nerve (ON) head and initial portion after the experimental increase in intraocular pressure (IOP). Material and methodsWistar rats underwent cauterization of three episcleral veins, which produced an immediate increase in the IOP, and was maintained for 3 months. Sagittal sections of the eyeball were studied with immunohistochemical techniques, using a primary antibody to GLUT-1. The GLUT-1 positive capillaries were counted, and measurements were made of the area, perimeter and mean diameter. ResultsMicroscopic examination of sections of the ON of control rats revealed a lower density and larger caliber of capillaries in the prelaminar region as compared with the other regions of the OP (p<.05). Comparison between the control and the experimental groups showed a reduction in capillary density (except in the prelaminar region) and a smaller size in all the areas of the OP studied, but less evident in the initial portion (p<.05). ConclusionsThe increase in IOP was associated with significant qualitative and quantitative changes in the capillaries of the laminar and poslaminar regions of the OP head. These changes appear to return toward parameters compatible with normality in the initial portion of the OP, an area where the vascular collapse was less evident. These findings might explain the significant reduction in ocular blood flow seen in patients with primary open-angle glaucoma.

Cambios morfológicos y morfométricos en los capilares del nervio óptico de rata en un modelo experimental de glaucoma

AimTo study the morphological and morphometric changes produced in the capillaries of the optic nerve (ON) head and initial portion after the experimental increase in intraocular pressure (IOP). Material and methodsWistar rats underwent cauterization of three episcleral veins, which produced an immediate increase in the IOP, and was maintained for 3 months. Sagittal sections of the eyeball were studied with immunohistochemical techniques, using a primary antibody to GLUT-1. The GLUT-1 positive capillaries were counted, and measurements were made of the area, perimeter and mean diameter. ResultsMicroscopic examination of sections of the ON of control rats revealed a lower density and larger caliber of capillaries in the prelaminar region as compared with the other regions of the ON (P<.05). Comparison between the control and the experimental groups showed a reduction in capillary density (except in the prelaminar region) and a smaller size in all the areas of the ON studied, but less evident in the initial portion (P<.05). ConclusionsThe increase in IOP was associated with significant qualitative and quantitative changes in the capillaries of the laminar and poslaminar regions of the ON head. These changes appear to return towards parameters compatible with normality in the initial portion of the ON, an area where the vascular collapse was less evident. These findings might explain the significant reduction in ocular blood flow seen in patients with primary open-angle glaucoma.