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Purpose: To clarify the optic nerve head (ONH) gene expression responses associated with a single, axon-damaging exposure to elevated IOP in relation to the composite cellular events previously identified in models of chronically elevated IOP. Methods: Anesthetized rats were exposed unilaterally to an 8-hour pulse-train controlled elevation of IOP (PT-CEI) at 60 mm Hg, while others received normotensive CEI at 20 mm Hg. ONH RNA was harvested at 0 hours and 1, 2, 3, 7, and 10 days after either CEI and from naïve animals. RNA sequencing was performed to analyze ONH gene expression. DAVID Bioinformatics tools were used to identify significant functional annotation clusters. Gene function was compared between PT-CEI and two models of chronic ocular hypertension from the literature. Results: The number of significantly changed genes peaked immediately (n = 1354) after PT-CEI (0 hours). This was followed by a lull (<4 genes per time point) at 1 and 2 days after PT-CEI. Gene activity increased again at 3 days (136 genes) and persisted at 7 (78 genes) and 10 (339 genes) days. Significant gene functional categories included an immediate upregulation of Defense Response at 0 hours, followed by upregulation in Cell Cycle, a reduction in Axonal-related genes at 3 to 10 days, and upregulation of Immune Response-related genes at 10 days following PT-CEI. The most commonly upregulated gene expression across our PT-CEI study and two chronic models of ocular hypertension were cell cycle related. Conclusions: The PT-CEI model places in sequence ONH gene expression responses previously reported in models with chronically elevated IOP and may provide insights into their role in optic nerve damage.

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Borderline personality disorder symptoms (BPDsx) in mothers have been linked to psychopathology in their offspring. However, it is still unclear whether BPDsx in fathers influences offspring psychopathology and, if so, how this risk transmission may occur. A total of 448 father-mother-offspring triads completed a longitudinal study following children from birth until age 20 and included self-report questionnaires and clinical interviews when children were 15 and 20 years old. Results revealed that paternal BPDsx were predictive of youth BPDsx and internalizing symptoms, even after controlling for maternal BPDsx. Chronic family stress was a significant mediator of the relationship between paternal BPDsx and offspring BPDsx, internalizing symptoms, and externalizing symptoms. Fathers' expressed emotion and child temperament were not significant mediators. Although offspring sex predicted youth outcomes, it was not a significant moderator of the association between paternal BPDsx and offspring symptoms. Finally, controlling for comorbid paternal disorders weakened the association between paternal BPDsx and youth psychopathology.

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Purpose: We previously reported increased expression of cell proliferation and Jak-Stat pathway-related genes in chronic experimental glaucoma model optic nerve heads (ONH) with early, mild injury. Here, we confirm these observations by localizing, identifying, and quantifying ONH cellular proliferation and Jak-Stat pathway activation in this model. Methods: Chronic intraocular pressure (IOP) elevation was achieved via outflow pathway sclerosis. After 5 weeks, ONH longitudinal sections were immunolabeled with proliferation and cell-type markers to determine nuclear densities in the anterior (unmyelinated) and transition (partially myelinated) ONH. Nuclear pStat3 labeling was used to detect Jak-Stat pathway activation. Nuclear density differences between control ONH (uninjected) and ONH with either early or advanced injury (determined by optic nerve injury grading) were identified by ANOVA. Results: Advanced injury ONH had twice the nuclear density (P < 0.0001) of controls and significantly greater astrocyte density in anterior (P = 0.0001) and transition (P = 0.006) ONH regions. An increased optic nerve injury grade positively correlated with increased microglia/macrophage density in anterior and transition ONH (P < 0.0001, both). Oligodendroglial density was unaffected. In glaucoma model ONH, 80% of anterior and 66% of transition region proliferating cells were astrocytes. Nuclear pStat3 labeling significantly increased in early injury anterior ONH, and 95% colocalized with astrocytes. Conclusions: Astrocytes account for the majority of proliferating cells, contributing to a doubled nuclear density in advanced injury ONH. Jak-Stat pathway activation is apparent in the early injury glaucoma model ONH. These data confirm dramatic astrocyte cell proliferation and early Jak-Stat pathway activation in ONH injured by elevated IOP.

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Purpose: Optic nerve head (ONH) astrocytes provide support for axons, but exhibit structural and functional changes (termed reactivity) in a number of glaucoma models. The purpose of this study was to determine if ONH astrocyte structural reactivity is axon-dependent. Methods: Using rats, we combine retrobulbar optic nerve transection (ONT) with acute controlled elevation of intraocular pressure (CEI), to induce total optic nerve axon loss and ONH astrocyte reactivity, respectively. Animals were euthanized immediately or 1 day post CEI, in the presence or absence of ONT. ONH sections were labeled with fluorescent-tagged phalloidin and antibodies against ß3 tubulin, phosphorylated cortactin, phosphorylated paxillin, or complement C3. ONH label intensities were quantified after confocal microscopy. Retrobulbar nerves were assessed for axon injury by light microscopy. Results: While ONT alone had no effect on ONH astrocyte structural orientation, astrocytes demonstrated significant reorganization of cellular extensions within hours after CEI, even when combined with ONT. However, ONH astrocytes displayed differential intensities of actin (phosphorylated cortactin) and focal adhesion (phosphorylated paxillin) mediators in response to CEI alone, ONT alone, or the combination of CEI and ONT. Lastly, label intensities of complement C3 within the ONH were unchanged in eyes subjected to CEI alone, ONT alone, or the combination of CEI and ONT, relative to controls. Conclusions: Early ONH astrocyte structural reactivity to elevated IOP is multifaceted, displaying both axon dependent and independent responses. These findings have important implications for pursuing astrocytes as diagnostic and therapeutic targets in neurodegenerative disorders with fluctuating levels of axon injury.

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Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.

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Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH. Cyt D delivery was quantified by liquid chromatography and mass spectrometry of isolated optic nerve tissue. One day after Cyt D delivery, anterior ONH filamentous actin bundle content was significantly reduced as assessed by fluorescent-tagged phalloidin labeling, relative to sham delivery. Anterior ONH nuclear counts and axon-specific beta-3 tubulin levels, as well as peripapillary retinal ganglion cell layer nuclear counts were not significantly altered after Cyt D delivery relative to sham delivery. Lastly, the surgical delivery technique caused minimal observable axon degeneration up to 10 days post-surgery. This small molecule delivery technique provides a new approach to studying optic neuropathies in in vivo rodent models.

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A reliable method of creating chronic elevation of intraocular pressure (IOP) in rodents is an important tool in reproducing and studying the mechanisms of optic nerve injury that occur in glaucoma. In addition, such a model could provide a valuable method for testing potential neuroprotective treatments. This paper outlines the basic methods for producing obstruction of aqueous humor outflow and IOP elevation by injecting hypertonic saline (a sclerosant) into the aqueous outflow pathway. This is one of several rodent glaucoma models in use today. In this method, a plastic ring is placed around the equator of the eye to restrict injected saline to the limbus. By inserting a small glass microneedle in an aqueous outflow vein in the episclera and injecting hypertonic saline toward the limbus, the saline is forced into Schlemm's canal and across the trabecular meshwork. The resultant inflammation and scarring of the anterior chamber angle occurs gradually, resulting in a rise in IOP after approximately 1 week. This article will describe the equipment necessary for producing this model and the steps of the technique itself.

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MicroRNAs are small, endogenous noncoding RNAs that modulate post-transcriptional gene expression. Recent evidence suggests that they may have a potential role in the regulation of the complex biological responses that develop in response to elevated intraocular pressure. However, contemporary microRNA assay techniques (e.g., microarrays and next-generation sequencing) typically require large amounts of RNA template that are often times difficult to obtain from glaucomatous tissue. We describe in detail an experimental protocol utilizing targeted pre-amplification and low-density polymerase chain reaction arrays to circumvent this hurdle. This approach optimizes the simultaneous high-throughput screening of small tissue samples, such as the rodent optic nerve head, for up to 754 microRNA probes while also providing an opportunity for subsequent confirmatory reactions of technical or biological replicates.

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Understanding the cellular pathways activated by elevated intraocular pressure (IOP) is crucial for the development of more effective glaucoma treatments. Microarray studies have previously been used to identify several key gene expression changes in early and extensively injured ONH, as well as in the retina. Limitations of microarrays include that they can only be used to detect transcripts that correspond to existing genomic sequencing information and their narrower dynamic range. However, RNA sequencing (RNA-seq) is a powerful tool for investigating known transcripts, as well as for exploring new ones (including noncoding RNAs and small RNAs), is more quantitative, and has the added benefit that the data can be re-analyzed as new sequencing information becomes available. Here, we describe an RNA-seq method specifically developed for identifying differentially expressed genes in optic nerve heads of eyes exposed to elevated intraocular pressure. The methods described here could also be applied to small tissue samples (less than 100 ng in total RNA yield) from retina, optic nerve, or other regions of the central nervous system.

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PURPOSE: To compare the effect of elevated intraocular pressure (IOP) on retinal capillary filling in elderly vs adult rats using optical coherence tomography angiography (OCTA). METHODS: The IOP of elderly (24-month-old, N=12) and adult (6-8month-old, N=10) Brown Norway rats was elevated in 10mmHg increments from 10 to 100mmHg. At each IOP level, 3D OCT data were captured using an optical microangiography (OMAG) scanning protocol and then post-processed to obtain both structural and vascular images. Mean arterial blood pressure (MAP), respiratory rate, pulse and blood oxygen saturation were monitored non-invasively throughout each experiment. Ocular perfusion pressure (OPP) was calculated as the difference between MAP for each animal and IOP at each level. The capillary filling index (CFI), defined as the ratio of area occupied by functional capillary vessels to the total scan area but excluding relatively large vessels of >30µm, was calculated at each IOP level and analyzed using the OCTA angiograms. Relative CFI vs IOP was plotted for the group means. CFI vs OPP was plotted for every animal in each group and data from all animals were combined in a CFI vs OPP scatter plot comparing the two groups. RESULTS: The MAP in adult animals was 108±5mmHg (mean±SD), whereas this value in the elderly was 99±5mmHg. All other physiologic parameters for both age groups were uniform and stable. In elderly animals, significant reduction of the CFI was first noted at IOP 40mmHg, as opposed to 60mmHg in adult animals. Individual assessment of CFI as a function of OPP for adult animals revealed a consistent plateau until OPP reached between 40 and 60mmHg. Elderly individuals demonstrated greater variability, with many showing a beginning of gradual deterioration of CFI at an OPP as high as 80mmHg. Overall comparison of CFI vs OPP between the two groups was not statistically significant. CONCLUSIONS: Compared to adults, some, but not all, elderly animals demonstrate a more rapid deterioration of CFI vs OPP. This suggests a reduced autoregulatory capacity that may contribute to increased glaucoma susceptibility in some older individuals. This variability must be considered when studying the relationship between IOP, ocular perfusion and glaucoma in elderly animal models.

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Purpose: MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that have been detected in human aqueous humor (AH). Prior studies have pooled samples to obtain sufficient quantities for analysis or used next-generation sequencing. Here, we used PCR arrays with preamplification to identify and compare miRNAs from individual AH samples between patients with primary open-angle glaucoma (POAG) and normal controls. Methods: AH was collected before cataract surgery from six stable, medically treated POAG patients and eight age-matched controls. Following reverse transcription and preamplification, individual patient samples were profiled on Taqman Low Density MicroRNA Array Cards. Differentially expressed miRNAs were stratified for fold changes larger than ±2 and for significance of P < 0.05. Significant Kyoto Encyclopedia of Genes and Genomes pathways influenced by the differentially expressed miRNAs were identified using the predicted target module of the miRWalk 2.0 database. Results: This approach detected 181 discrete miRNAs, which were consistently expressed across all samples of both experimental groups. Significant up-regulation of miR-518d and miR-143, and significant down-regulation of miR-660, was observed in the AH of POAG patients compared with controls. These miRNAs were predicted to reduce cell proliferation and extracellular matrix remodeling, endocytosis, Wnt signaling, ubiquitin-mediated proteolysis, and adherens junction function. Conclusions: This pilot study demonstrates that miRNA expression within the AH of POAG patients differs from age-matched controls. AH miRNAs exhibit potential as biomarkers of POAG, which merits further investigation in a larger case-controlled study. This technique provides a cost-effective and sensitive approach to assay miRNAs in individual patient samples without the need for pooling.

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Purpose: We determine if several hours of controlled elevation of IOP (CEI) will produce the optic nerve head (ONH) gene expression changes and optic nerve (ON) damage pattern associated with early experimental glaucoma in rats. Methods: The anterior chambers of anesthetized rats were cannulated and connected to a reservoir to elevate IOP. Physiologic parameters were monitored. Following CEI at various recovery times, ON cross-sections were graded for axonal injury. Anterior ONHs were collected at 0 hours to 10 days following CEI and RNA extracted for quantitative PCR measurement of selected messages. The functional impact of CEI was assessed by electroretinography (ERG). Results: During CEI, mean arterial pressure (99 ± 6 mm Hg) and other physiologic parameters remained stable. An 8-hour CEI at 60 mm Hg produced significant focal axonal degeneration 10 days after exposure, with superior lesions in 83% of ON. Message analysis in CEI ONH demonstrated expression responses previously identified in minimally injured ONH following chronic IOP elevation, as well as their sequential patterns. Anesthesia with cannulation at 20 mm Hg did not alter these message levels. Electroretinographic A- and B-waves, following a significant reduction at 2 days after CEI, were fully recovered at 2 weeks, while peak scotopic threshold response (pSTR) remained mildly but significantly depressed. Conclusions: A single CEI reproduces ONH message changes and patterns of ON injury previously observed with chronic IOP elevation. Controlled elevation of IOP can allow detailed determination of ONH cellular and functional responses to an injurious IOP insult and provide a platform for developing future therapeutic interventions.

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Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in response to uncontrolled intraocular pressure (IOP). The temporal response of ONH astrocytes (glial cells responsible for axonal support) to elevated IOP remains unknown. Here, we evaluate the response of actin-based astrocyte extensions and integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using anterior chamber cannulation connected to a saline reservoir. ONH astrocytic extension orientation was significantly and regionally rearranged immediately after IOP elevation (inferior ONH, 43.2° ± 13.3° with respect to the anterior-posterior axis versus 84.1° ± 1.3° in controls, p<0.05), and re-orientated back to baseline orientation 1 day post IOP normalization. ONH axonal microtubule filament label intensity was significantly reduced 1 and 3 days post IOP normalization, and returned to control levels on day 5. Phosphorylated focal adhesion kinase (FAK) levels steadily decreased after IOP normalization, while levels of phosphorylated paxillin (a downstream target of FAK involved in focal adhesion dynamics) were significantly elevated 5 days post IOP normalization. The levels of phosphorylated cortactin (a downstream target of Src kinase involved in actin polymerization) were significantly elevated 1 and 3 days post IOP normalization and returned to control levels by day 5. No significant axon degeneration was noted by morphologic assessment up to 5 days post IOP normalization. Actin-based astrocyte structure and signaling within the ONH are significantly altered within hours after IOP elevation and prior to axonal cytoskeletal rearrangement, producing some responses that recover rapidly and others that persist for days despite IOP normalization.

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OBJECTIVE: There has been much newspaper and online news coverage of in-flight obstetric births on commercial aircraft over several decades. This case series reviews several cases of in-flight birth and immediate maternal and neonatal outcomes from air medical retrievals in the Northern Territory of Australia over a 4-year [corrected] period. METHODS: This is a retrospective written case note and electronic medical retrieval record analysis of 4 patients undergoing in-flight, at altitude, obstetric birth. RESULTS: Four premature births are recorded by CareFlight Operations over a 4-year period from January 2011 to January 2015. All patients involved were preterm; term ranged from 22 weeks to 36 weeks. Tocolysis was implemented on all 4 patients according to local obstetric guidelines. Maternal complications included 1 patient suffering antepartum hemorrhage and 2 patients suffering postpartum hemorrhage. Three neonates born at altitude needed neonatal resuscitation including positive-pressure ventilation. One neonate, 22 weeks' gestation, died approximately 2 hours after delivery. Maternal follow-up showed no morbidity or mortality at 1 to 6 days after birth. CONCLUSION: In-flight deliveries are rare events in air medical medicine. This case series includes patients of variable preterm gestation and correlates poor outcomes to prematurity of neonates. Close communication between remote clinics, obstetric centers, and air medical teams plus up-to-date early labor guidelines are essential for safe practice and to limit the risk of in-flight births.

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PURPOSE: To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). METHODS: Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. RESULTS: Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p < 0.0022), and in 7 of 8 EG eyes (p < 0.005). In at least 5 EG eyes, significant expansions (p < 0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). CONCLUSION: In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye.

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PURPOSE: To determine if retinal capillary filling is preserved in the face of acutely elevated intraocular pressure (IOP) in anesthetized rats, despite a reduction in total retinal blood flow (RBF), using optical microangiography/optical coherence tomography (OMAG/OCT). METHODS: OMAG provided the capability of depth-resolved imaging of the retinal microvasculature down to the capillary level. Doppler OCT was applied to measure the total RBF using an enface integration approach. The microvascular pattern, capillary density, and total RBF were monitored in vivo as the IOP was increased from 10 to 100mmHg in 10mmHg intervals and returned back to 10mmHg. RESULTS: In animals with mean arterial pressure (MAP) of 102±4mmHg (n=10), when IOP was increased from 0 to 100mmHg, the capillary density remained at or above 80% of baseline for the IOP up to 60mmHg [or ocular perfusion pressure (OPP) at 40mmHg]. This was then decreased, achieving 60% of baseline at IOP 70mmHg and OPP of 30mmHg. Total RBF was unaffected by moderate increases in IOP up to 30mmHg, beyond which total RBF decreased linearly, reaching 50% of baseline at IOP 60mmHg and OPP 40mmHg. Both capillary density and total RBF were totally extinguished at 100mmHg, but fully recovered when IOP returned to baseline. By comparison, a separate group of animals with lower MAP (mean=75±6mmHg, n=7) demonstrated comparable decreases in both capillary filling and total RBF at IOPs that were 20mmHg lower than in the initial group. Both were totally extinguished at 80mmHg, but fully recovered when IOP returned to baseline. Relationships of both parameters to OPP were unchanged. CONCLUSION: Retinal capillary filling and total RBF responses to IOP elevation can be monitored non-invasively by OMAG/OCT and both are influenced by OPP. Retinal capillary filling was relatively preserved down to a perfusion pressure of 40mmHg, despite a linear reduction in total RBF.

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PURPOSE: The cellular mechanisms linking elevated IOP with glaucomatous damage remain unresolved. Mechanical strains and short-term increases in IOP can trigger ATP release from retinal neurons and astrocytes, but the response to chronic IOP elevation is unknown. As excess extracellular ATP can increase inflammation and damage neurons, we asked if sustained IOP elevation was associated with a sustained increase in extracellular ATP in the posterior eye. METHODS: No ideal animal model of chronic glaucoma exists, so three different models were used. Tg-Myoc(Y437H) mice were examined at 40 weeks, while IOP was elevated in rats following injection of hypertonic saline into episcleral veins and in cynomolgus monkeys by laser photocoagulation of the trabecular meshwork. The ATP levels were measured using the luciferin-luciferase assay while levels of NTPDase1 were assessed using qPCR, immunoblots, and immunohistochemistry. RESULTS: The ATP levels were elevated in the vitreal humor of rats, mice, and primates after a sustained period of IOP elevation. The ecto-ATPase NTPDase1 was elevated in optic nerve head astrocytes exposed to extracellular ATP for an extended period. NTPDase1 was also elevated in the retinal tissue of rats, mice, and primates, and in the optic nerve of rats, with chronic elevation in IOP. CONCLUSIONS: A sustained elevation in extracellular ATP, and upregulation of NTPDase1, occurs in the posterior eye of rat, mouse, and primate models of chronic glaucoma. This suggests the elevation in extracellular ATP may be sustained in chronic glaucoma, and implies a role for altered purinergic signaling in the disease.

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Injection of hypertonic saline via episcleral veins toward the limbus in laboratory rats can produce elevated intraocular pressure (IOP) by sclerosis of aqueous humor outflow pathways. This article describes important anatomic characteristics of the rat optic nerve head (ONH) that make it an attractive animal model for human glaucoma, along with the anatomy of rat aqueous humor outflow on which this technique is based. The injection technique itself is also described, with the aid of a supplemental movie, including necessary equipment and specific tips to acquire this skill. Outcomes of a successful injection are presented, including IOP elevation and patterns of optic nerve injury. These concepts are then specifically considered in light of the use of this model to assess potential neuroprotective therapies. Advantages of the hypertonic saline model include a delayed and relatively gradual IOP elevation, likely reproduction of scleral and ONH stresses and strains that may be important in producing axonal injury, and its ability to be applied to any rat (and potentially mouse) strain, leaving the unmanipulated fellow eye as an internal control. Challenges include the demanding surgical skill required by the technique itself, a wide range of IOP response, and mild corneal clouding in some animals. However, meticulous application of the principles detailed in this article and practice will allow most researchers to attain this useful skill for studying cellular events of glaucomatous optic nerve damage.

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The purpose of this study is to three-dimensionally (3D) characterize the principal macroscopic and microscopic relationships within the rat optic nerve head (ONH) and quantify them in normal control eyes. Perfusion-fixed, trephinated ONH from 8 normal control eyes of 8 Brown Norway Rats were 3D histomorphometrically reconstructed, visualized, delineated and parameterized. The rat ONH consists of 2 scleral openings, (a superior neurovascular and inferior arterial) separated by a thin connective tissue strip we have termed the "scleral sling". Within the superior opening, the nerve abuts a prominent extension of Bruch's Membrane (BM) superiorly and is surrounded by a vascular plexus, as it passes through the sclera, that is a continuous from the choroid into and through the dural sheath and contains the central retinal vein (CRV), (inferiorly). The inferior scleral opening contains the central retinal artery and three long posterior ciliary arteries which obliquely pass through the sclera to obtain the choroid. Bruch's Membrane Opening (BMO) is irregular and vertically elongated, enclosing the nerve (superiorly) and CRV and CRA (inferiorly). Overall mean BMO Depth, BMO Area, Choroidal Thickness and peripapillary Scleral Thickness were 29 µm, 56.5 × 10(3) µm(2), 57 µm and 104 µm respectively. Mean anterior scleral canal opening (ASCO) and posterior scleral canal opening (PSCO) radii were 201 ± 15 µm and 204 ± 16 µm, respectively. Mean optic nerve area at the ASCO and PSCO were 46.3 × 10(3)±4.4 × 10(3) µm(2) and 44.1 × 10(3)±4.5 × 10(3) µm(2) respectively. In conclusion, the 3D complexity of the rat ONH and the extent to which it differs from the primate have been under-appreciated within previous 2D studies. Properly understood, these anatomic differences may provide new insights into the relative susceptibilities of the rat and primate ONH to elevated intraocular pressure.

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