In vivo optic nerve head mechanical response to intraocular and cerebrospinal fluid pressure: imaging protocol and quantification method.
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ABSTRACT:
SUBMITTER: Fazio MA
PROVIDER: S-EPMC6107503 | biostudies-literature | 2018 Aug
REPOSITORIES: biostudies-literature
Publications
In vivo optic nerve head mechanical response to intraocular and cerebrospinal fluid pressure: imaging protocol and quantification method.
Fazio Massimo A MA Clark Mark E ME Bruno Luigi L Girkin Christopher A CA
Scientific reports 20180823 1
This study presents a quantification method for the assessment of the optic nerve head (ONH) deformations of the living human eye under acute intraocular pressure (IOP) elevation and change of cerebrospinal fluid pressure (CSFP) with body position. One eye from a brain-dead organ donor with open-angle glaucoma was imaged by optical coherence tomography angiography during an acute IOP and CSFP elevation test. Volumetric 3D strain was computed by digital volume correlation. With increase in IOP th ...[more]
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Project description:Purpose:To model the sensitivity of the optic nerve head (ONH) biomechanical environment to acute variations in IOP, cerebrospinal fluid pressure (CSFP), and central retinal artery blood pressure (BP). Methods:We extended a previously published numerical model of the ONH to include 24 factors representing tissue anatomy and mechanical properties, all three pressures, and constraints on the optic nerve (CON). A total of 8340 models were studied to predict factor influences on 98 responses in a two-step process: a fractional factorial screening analysis to identify the 16 most influential factors, followed by a response surface methodology to predict factor effects in detail. Results:The six most influential factors were, in order: IOP, CON, moduli of the sclera, lamina cribrosa (LC) and dura, and CSFP. IOP and CSFP affected different aspects of ONH biomechanics. The strongest influence of CSFP, more than twice that of IOP, was on the rotation of the peripapillary sclera. CSFP had similar influence on LC stretch and compression to moduli of sclera and LC. On some ONHs, CSFP caused large retrolamina deformations and subarachnoid expansion. CON had a strong influence on LC displacement. BP overall influence was 633 times smaller than that of IOP. Conclusions:Models predict that IOP and CSFP are the top and sixth most influential factors on ONH biomechanics. Different IOP and CSFP effects suggest that translaminar pressure difference may not be a good parameter to predict biomechanics-related glaucomatous neuropathy. CON may drastically affect the responses relating to gross ONH geometry and should be determined experimentally.
| S-EPMC5769499 | biostudies-literature
Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury. Six- to eight-week old C57Bl/6 male mice were used in this experiment. One eye underwent an elevation in intraocular pressure to 30 mmHg for 1 hour and then allowed to recover for 3 days. The contralateral eye served as a control. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. We used 10 mice to generate five biological replicates for each condition.
2013-05-17 | E-GEOD-40009 | biostudies-arrayexpress
Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury.
2013-05-17 | GSE40009 | GEO
Project description:Intraocular pressure (IOP) is an important risk factor for glaucoma, and the response of the ONH and surrounding tissues to elevated IOP are often investigated to better understand pathophysiology. In vivo structure including that of the optic nerve head (ONH) and surrounding tissue of the eye are often assessed using optical coherence tomography (OCT). With advances in OCT technology, both large vessels and capillaries can be imaged non-invasively (OCT Angiography). Because a significant portion of retinal thickness is comprised of vasculature, the purpose of the current study was to investigate OCT structural and vascular changes in healthy non-human primate eyes with systematic graded increases and decreases in IOP. Six healthy animals with no previous experimental intervention were used. The pressure in the anterior chamber was adjusted from 10?mmHg to 60?mmHg and back to 10?mmHg in 10?mmHg steps every 10?min. Using optical coherence tomography (OCT), retinal nerve fiber layer (RNFL) thickness, minimum rim width (MRW), Bruch's membrane opening (BMO) size and relative height, anterior lamina cribrosa surface (ALCS) depth, choroidal thickness, and angiography (OCTA) were quantified. With IOP challenge there were significant changes in all morphological measures quantified (p?<?0.01) other than BMO size (p?=?0.30) and RNFL thickness (p?=?0.29). Specifically, the position of the BMO was sensitive to both an increase and decease in IOP. The inner retinal capillary density gradually decreased with increasing IOP, reaching statistical significance when pressure exceeded 50?mmHg, but returned when IOP was reduced. The average choroidal thickness around the ONH decreased for elliptical annuli 500-1000??m and 1000-1500??m, from the BMO, with increasing IOP (p?<?0.01). For the 1000-1500??m annulus, choroid thickness did not return to baseline with IOP reduction. Similarly, the MRW decreased with increase in IOP, but with pressure reduction did not return, and at the final 10?mmHg time point was thinner than at baseline (p?<?0.01). The results from this experiment illustrate differences in ONH neural rim tissue, RNFL and vessel density changes with acute IOP challenge. Overall, vessel collapse could not completely account for changes in RNFL or ONH MRW thickness. The study supports the hypothesis neural rim compression may be an important part of IOP-induced damage.
| S-EPMC5878999 | biostudies-literature
Project description:The time course of the changes in the optic nerve head (ONH) blood flow in response to changes in the ocular perfusion pressure (OPP) induced by an artificial elevation of the intraocular pressure (IOP) has not been determined. We measured the blood flow, represented by the mean blur rate (MBR), on the ONH determined by laser speckle flowgraphy. The MBR was determined before, during, and after the IOP was elevated by 20 or 30?mmHg by pressure applied on the eye by an ophthalmodynamometer in a total of 27 healthy eyes. For an IOP elevation of 20?mmHg, the percentage reduction in the MBR-vessel was -24.7%, and in the MBR-tissue was -16.0% (P?<?0.001). For an IOP elevation of 30?mmHg, the percentage reduction of the MBR-vessel was -35.3% and the MBR-tissue was -24.7% (P?<?0.001). During the 30?mmHg IOP elevation for 10?minutes, both the MBR-vessel and MBR-tissue began returning to the baseline level from 1?minute after the beginning of the IOP elevation (P?<?0.01, P?<?0.05, respectively) and continued returning during the 10?minutes IOP elevation (P?<?0.001, P?<?0.01, respectively). We conclude that the ONH can autoregulate its blood flow in response to experimental changes in OPP induced by IOP elevations.
| S-EPMC6250699 | biostudies-literature
Project description:Axonal transport blockade is an initial step in retinal ganglion cell (RGC) degeneration in glaucoma and targeting maintenance of normal axonal transport could confer neuroprotection. We present an objective, quantitative method for assessing axonal transport blockade in mouse glaucoma models. Intraocular pressure (IOP) was elevated unilaterally in CD1 mice for 3 days using intracameral microbead injection. Longitudinal sections of optic nerve head (ONH) were immunofluorescently labeled for myelin basic protein (MBP) and amyloid precursor protein (APP), which is transported predominantly orthograde by neurons. The beginning of the myelin transition zone, visualized with the MBP label, was more posterior with elevated IOP, 288.8 ± 40.9 μm, compared to normotensive control eyes, 228.7 ± 32.7 μm (p = 0.030, N = 6 pairs). Glaucomatous regional APP accumulations in retina, prelaminar ONH, unmyelinated ONH, and myelinated optic nerve were identified by objective qualification of pixels with fluorescent intensity greater than the 97.5th percentile value of control eyes (suprathreshold pixels). This method segregated images with APP blockade from those with normal transport of APP. The fraction of suprathreshold pixels was significantly higher following IOP elevation than in normotensive controls in the unmyelinated ONH and myelinated nerve regions (paired analyses, p = 0.02 and 0.003, respectively, N = 12), but not in retina or prelaminar ONH (p = 0.91 and 0.08, respectively). The mean intensity of suprathreshold pixels was also significantly greater in glaucoma than in normotensive controls in prelaminar ONH, unmyelinated ONH and myelinated optic nerve (p = 0.01, 0.01, 0.002, respectively). Using this method, subconjunctival glyceraldehyde, which is known to worsen long-term RGC loss with IOP elevation, also produced greater APP blockade, but not statistically significant compared to glaucoma alone. Systemic losartan, which aids RGC axonal survival in glaucoma, reduced APP blockade, but not statistically significant compared to glaucoma alone. The method provides a short-term assessment of axonal injury for use in initial tests of neuroprotective therapies that may beneficially affect RGC transport in animal models of glaucoma.
| S-EPMC7335019 | biostudies-literature
Project description:PurposeCerebrospinal fluid pressure (CSFp) changes are involved or implicated in various ocular conditions including glaucoma, idiopathic intracranial hypertension, and visual impairment and intracranial pressure syndrome. However, little is known about the effects of CSFp on lamina cribrosa and retrolaminar neural tissue (RLNT) biomechanics, potentially important in these conditions. Our goal was to use an experimental approach to visualize and quantify the deformation of these tissues as CSFp increased.MethodsThe posterior eye and RLNT of porcine eyes (n = 3) were imaged using synchrotron radiation phase-contrast micro-computed tomography (PC ?CT) at an intraocular pressure of 15 mm Hg and CSFps of 4, 10, 20, and 30 mm Hg. Scans of each tissue region were acquired at each CSFp step and analyzed using digital volume correlation to determine 3-dimensional tissue deformations.ResultsElevating CSFp increased the strain in the lamina cribrosa and RLNT of all three specimens, with the largest strains occurring in the RLNT. Relative to the baseline CSFp of 4 mm Hg, at 30 mm Hg, the lamina cribrosa experienced a mean first and third principal strain of 4.4% and -3.5%, respectively. The corresponding values for the RLNT were 9.5% and -9.1%.ConclusionsCSFp has a significant impact on the strain distributions within the lamina cribrosa and, more prominently, within the RLNT. Elevations in CSFp were positively correlated with increasing deformations in each region and may play a role in ocular pathologies linked to changes in CSFp.
| S-EPMC6733531 | biostudies-literature
Project description: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 ?3 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.
| S-EPMC6343680 | biostudies-other
Project description:In glaucoma, the optic nerve head (ONH) is the likely site of initial injury and elevated intraocular pressure (IOP) is the best-known risk factor. This study determines global gene expression changes in the pressure-injured ONH.Unilateral sustained IOP elevation (glaucoma, n = 46) or optic nerve transection (n = 10) was produced in rats. ONHs were removed, and the retrobulbar optic nerves were graded for degeneration. Gene expression in the glaucomatous ONH with extensive injury was compared with that in the fellow ONH (n = 6/group), by using cDNA microarrays. Data from 12 arrays were normalized, significant differences in gene expression determined, and significantly affected gene classes identified. For the remaining ONH, grouped by experimental condition and degree of injury, quantitative reverse transcriptase-PCR (qPCR) and ANOVA were used to compare selected message levels.Microarray analysis identified more than 2000 significantly regulated genes. For 225 of these genes, the changes were greater than twofold. The most significantly affected gene classes were cell proliferation, immune response, lysosome, cytoskeleton, extracellular matrix, and ribosome. A 2.7-fold increase in ONH cellularity confirmed glaucoma model cell proliferation. By qPCR, increases in levels of periostin, collagen VI, and transforming growth factor beta1 were linearly correlated to the degree of IOP-induced injury. For cyclinD1, fibulin 2, tenascin C, TIMP1, and aquaporin-4, correlations were significantly nonlinear, displaying maximum change with focal injury.In the ONH, pressure-induced injury results in cell proliferation and dramatically altered gene expression. For specific genes, expression levels were most altered by focal injury, suggesting that further array studies may identify initial, and potentially injurious, altered processes.
| S-EPMC1950563 | biostudies-literature
Project description:ImportanceThe acute biomechanical response of the optic nerve head (ONH) to intraocular pressure (IOP) elevations may serve as a biomarker for the development and progression of glaucoma.ObjectiveTo evaluate the association between visual field loss and the biomechanical response of the ONH to acute transient IOP elevations.Design, setting, and participantsIn this observational study, 91 Chinese patients (23 with primary open-angle glaucoma [POAG], 45 with primary angle-closure glaucoma, and 23 without glaucoma) were recruited from September 3, 2014, through February 2, 2017. Optical coherence tomography scans of the ONH were acquired at baseline and at 2 sequential IOP elevations (0.64 N and then 0.90 N, by applying forces to the anterior sclera using an ophthalmodynamometer). In each optical coherence tomography volume, lamina cribrosa depth (LCD) and minimum rim width (MRW) were calculated. The mean deviation (MD) and the visual field index (VFI), as assessed by automated perimetry, were correlated with IOP-induced changes of LCD and MRW globally and sectorially.Main outcomes and measuresThe LCD, MRW, MD, and VFI.ResultsAmong the 91 patients, 39 (42.9%) were women; the mean (SD) age was 65.48 (7.23) years. In POAG eyes, a greater change in LCD (anterior displacement) was associated with worse MD and VFI (R = -0.64; 95% CI, -0.97 to -0.31; P = .001; and R = -0.57; 95% CI, -0.94 to -0.19; P = .005, respectively) at the first IOP elevation, and a greater reduction in MRW was also associated with worse MD and VFI (first IOP elevation: R = -0.48; 95% CI, -0.86 to -0.09; P = .02; and R = -0.57; 95% CI, -0.94 to -0.20; P = .004, respectively; second IOP elevation: R = -0.56; 95% CI, -0.98 to -0.13; P = .01; and R = -0.60; 95% CI, -1.03 to -0.17; P = .008, respectively), after adjusting for age, sex, and baseline IOP. A correlation was found between the reduction in MRW in the inferior-temporal sector and the corresponding visual field cluster in POAG eyes at the second elevation (? = -0.55; 95% CI, -0.78 to -0.18; P = .006).Conclusions and relevanceThe biomechanical response of the ONH to acute IOP elevations was associated with established visual field loss in POAG eyes, but not in primary angle-closure glaucoma eyes. This suggests that ONH biomechanics may be related to glaucoma severity in POAG and that the 2 glaucoma subgroups exhibit inherently different biomechanical properties.
| S-EPMC5838605 | biostudies-literature