Deformation of the Normal Monkey Optic Nerve Head Connective Tissue after Acute IOP Elevation within 3-D Histomorphometric Reconstructions

Purpose To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). Methods C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression, and transport block were also analyzed. Results B6 mice had abundant AQP4 expression in Müller cells, astrocytes of retina and myelinated ON (MON), but minimal AQP4in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p = 0.42) and axonal transport blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Conclusion Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.

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The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.15-17624 ◽

2015 ◽

Vol 56 (13) ◽

pp. 7661 ◽

Cited By ~ 23

Author(s):

Hongli Yang ◽

Ruojin Ren ◽

Howard Lockwood ◽

Galen Williams ◽

Vincent Libertiaux ◽

...

Keyword(s):

Optic Nerve ◽

Global Change ◽

Connective Tissue ◽

Optic Nerve Head ◽

Experimental Glaucoma

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The Role of Aquaporin-4 in Optic Nerve Head Astrocytes in Experimental Glaucoma

10.1101/2020.12.04.411322 ◽

2020 ◽

Author(s):

Elizabeth Kimball ◽

Julie Schaub ◽

Sarah Quillen ◽

Casey Keuthan ◽

Mary Ellen Pease ◽

...

Keyword(s):

Optic Nerve ◽

Optic Nerve Head ◽

Aquaporin 4 ◽

Ocular Tissue ◽

Tissue Sections ◽

Experimental Glaucoma ◽

Axon Loss ◽

Channel Expression ◽

Iop Elevation ◽

Bead Injection

AbstractPurposeTo study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null).MethodsC57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression & transport block was also analyzed.ResultsB6 mice presented abundant AQP4 in Müller cells, astrocytes of retina and myelinated ON (MON), but minimal expression in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p=0.42) and axonal transport blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6).ConclusionLack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.

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The Three-Dimensional Structure of the Connective Tissue in the Lamina Cribrosa of the Human Optic Nerve Head

Ophthalmologica ◽

10.1159/000310787 ◽

1997 ◽

Vol 211 (3) ◽

pp. 183-191 ◽

Cited By ~ 15

Author(s):

Mike Birch ◽

Daniel Brotchie ◽

Neil Roberts ◽

Ian Grierson

Keyword(s):

Optic Nerve ◽

Connective Tissue ◽

Optic Nerve Head ◽

Three Dimensional ◽

Lamina Cribrosa ◽

Dimensional Structure ◽

Three Dimensional Structure ◽

Human Optic Nerve

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Mechanical Deformation of Human Optic Nerve Head and Peripapillary Tissue in Response to Acute IOP Elevation

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.18-26071 ◽

2019 ◽

Vol 60 (4) ◽

pp. 913 ◽

Cited By ~ 12

Author(s):

Yanhui Ma ◽

Elias Pavlatos ◽

Keyton Clayson ◽

Xueliang Pan ◽

Sunny Kwok ◽

...

Keyword(s):

Optic Nerve ◽

Optic Nerve Head ◽

Mechanical Deformation ◽

Iop Elevation ◽

Human Optic Nerve

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Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Normal- and High-Tension Glaucoma Subjects

10.1101/2021.12.15.472712 ◽

2021 ◽

Author(s):

Thanadet Chuangsuwanich ◽

Tin Aung Tun ◽

Xiaofei Wang ◽

Zhi Yun Chin ◽

Satish Kumar Panda ◽

...

Keyword(s):

Optic Nerve ◽

Visual Field ◽

Optic Nerve Head ◽

Open Angle Glaucoma ◽

Visual Field Loss ◽

Temporal Region ◽

Retinal Sensitivity ◽

Cross Sectional ◽

High Tension ◽

Iop Elevation

Purpose: To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in glaucoma subjects. Design: Clinic based cross-sectional study. Participants: 229 subjects with primary open angle glaucoma (subdivided into 115 high tension glaucoma (HTG) subjects and 114 normal tension glaucoma (NTG) subjects). Methods: For one eye of each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. A 3-dimensional (3D) strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e. deformation) in each ONH. Strains in the pre-lamina tissue (PLT) and the retina, the choroid, the sclera and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec, Dublin, CA, USA). This was done globally, then locally according to the regionalization scheme of Garway-Heath et al. Main Outcome Measures: Associations between ONH strains and values of retinal sensitivity from visual field testing. Results: For HTG subjects, we found that (1) there were significant negative linear associations between ONH strains and retinal sensitivity (p<0.001) (on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 dB), (2) high strain regions co-localized with anatomically-mapped regions of high visual field loss, (3) the strongest negative associations were observed in the superior region and in the PLT. In contrast, for NTG subjects, no significant associations between strains and retinal sensitivity were observed except in the supero-temporal region of the LC. Conclusion: We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, HTG subjects who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend was in general less pronounced in NTG subjects, which could suggest a distinct pathophysiology between the two glaucoma subtypes.

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Adduction Induces Large Optic Nerve Head Deformations in Subjects with Normal Tension Glaucoma

10.1101/2021.08.25.457300 ◽

2021 ◽

Author(s):

Thanadet Chuangsuwanich ◽

Tin Aung Tun ◽

Xiaofei Wang ◽

Zhi Yun Chin ◽

Satish Kumar Panda ◽

...

Keyword(s):

Optic Nerve ◽

Optic Nerve Head ◽

Learning Algorithm ◽

Effective Strain ◽

Three Dimensional ◽

Normal Tension Glaucoma ◽

Cross Sectional ◽

Significant Difference ◽

Iop Elevation ◽

Pre Treatment

Purpose: To assess optic nerve head (ONH) deformations and strains during adduction, abduction, and intraocular pressure (IOP) elevation in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Design: Clinic-based cross-sectional study. Participants: 114 HTG subjects and 114 NTG subjects. Methods. We recruited 228 subjects (114 subjects with HTG [pre-treatment IOP > 21mmHg] and 114 with NTG [pre-treatment IOP < 21mmHg]). For each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degree adduction, (3) 20 degree abduction, and (4) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the prelaminar tissue (PLT), the choroid, the sclera and the lamina cribrosa (LC) using a deep learning algorithm. We also digitally aligned the OCT volumes obtained from (2)-(4) to the primary gaze volume (1) before performing digital volume correlation (DVC) analysis to quantify IOP- and gaze-induced ONH tissues three-dimensional displacements and effective strain (a local measure of tissue deformation) for all scenarios. Main Outcome Measures: Three-dimensional ONH displacements and strains. Results: Across all subjects, adduction generated high effective strain (4.2 +- 1.4%) in the ONH tissues with no significant difference (p>0.05) with those induced by IOP elevation (4.5 +- 1.5%); while abduction generated significantly lower (p = 0.014) effective strain (3.8 +- 1.1%). Interestingly, the LC of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG:4.6 +- 1.7% vs NTG:4.1 +- 1.5%, p = 0.047). Conversely, the LC tissue of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9 +- 1.9% vs HTG: 4.0 +- 1.4%, p = 0.041). Conclusion: We found that adduction produced comparable strains and displacements as IOP elevation. We also found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects - and that these differences were most pronounced in the LC tissue.

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