Dynamics, Alterations, and Consequences of Minimally Invasive Intraocular Pressure Elevation in Rats

Gramlich, Oliver W.; Lueckner, Theresa; Kriechbaum, Maren; Teister, Julia; Tao, Xue; Pein, Harald D. von; Pfeiffer, Norbert; Grus, Franz H.

doi:10.1167/iovs.13-12714

Cited by 16 publications

(21 citation statements)

References 35 publications

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“…Optic nerve neurodegeneration was accessed after p-phenylenediamine (PPD) staining of 0.7 µm semithin transverse optic nerve sections as described previously 55 . Briefly, six to seven images per optic nerve were captured in a crosswise procedure using 100x magnification (Olympus SPlan 100x/1.25 oil, 160/0.17, Olympus Deutschland GmbH, Hamburg, Germany) and an upright microscope (Olympus Vanox-T AH-2;) in accordance with a consistent orientation.…”

Section: Methodsmentioning

confidence: 99%

Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model

Teister

Anders

Beck

et al. 2017

Sci Rep

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Although elevated intraocular pressure (IOP) remains the major risk factor in glaucoma, neurodegenerative processes continue despite effective IOP lowering. Altered α-synuclein antibody (Abs) levels have been reported to play a crucial role. This study aimed at identifying whether α-synuclein Abs are capable to decelerate neuronal decay while providing insights into proteomic changes. Four groups of Sprague Dawley rats received episcleral vein occlusion: (1) CTRL, no intravitreal injection, n = 6, (2) CTRL IgG, intravitreal injection of unspecific IgG, n = 5, (3) Buffer, intravitreal injection of buffer, n = 6, (4), α-synuclein Ab, intravitreal injection of α-synuclein Ab, n = 5. IOP and retinal nerve fiber layer thickness (RNFLT) were monitored and immunohistochemistry, microarray and proteomic analysis were performed. RNFLT was reduced in CTRL, CTRL IgG and Buffer group (all p < 0.01) and α-synuclein Ab group (p = 0.17). Axon and RGC density showed an increased neurodegeneration in CTRL, CTRL IgG and Buffer group (all p < 0.01) and increased neuronal survival in α-synuclein Ab group (p = 0.38 and 0.06, respectively) compared with fellow eyes. Proteomic analysis revealed alterations of cofilin 1 and superoxide dismutase 1 expression. This data indicate that α-synuclein Ab might indirectly modulate the actin cytoskeleton organization and negatively regulate apoptotic processes via cofilin 1 and superoxide dismutase 1.

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Section: Methodsmentioning

confidence: 99%

Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model

Teister

Anders

Beck

et al. 2017

Sci Rep

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“…(Yang et al, 2012b) Gramlich et al found after chronic recurrent episodes of a short-duration IOP “spike” (1 hour each to 30–35 mmHg), there was a decline in total retinal thickness measured by SDOCT and RGC density measured histologically as well as an increase in the optic nerve axon damage grade. (Gramlich et al, 2014) Using longitudinal SDOCT imaging, Abbott et al found that RNFL loss occurred earlier and was more severe in older rats age 9.5-months as compared with younger rats aged 2-months despite similar exposure to chronic IOP elevation over 3-weeks. Abbott et al also reported that axonal transport disruption and optic nerve damage were substantially worse than RNFL thinning, especially in the older rats and confirmed by post mortem microscopy of retinal whole mounts that there was relative preservation of the intraretinal portion of RGC axons.…”

Section: Introductionmentioning

confidence: 99%

In vivo imaging methods to assess glaucomatous optic neuropathy

Fortune

2015

Experimental Eye Research

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The goal of this review is to summarize the most common imaging methods currently applied for in vivo assessment of ocular structure in animal models of experimental glaucoma with an emphasis on translational relevance to clinical studies of the human disease. The most common techniques in current use include optical coherence tomography and scanning laser ophthalmoscopy. In reviewing the application of these and other imaging modalities to study glaucomatous optic neuropathy, this article is organized into three major sections: 1) imaging the optic nerve head, 2) imaging the retinal nerve fiber layer and 3) imaging retinal ganglion cell soma and dendrites. The article concludes with a brief section on possible future directions.

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“…8,9 This minimally invasive technique employed the concept of oculopression to produce elevated IOP. [10][11][12] An advantage of the suture compression model is that it is not associated with ocular tissue penetration or traumatization, and therefore relatively preserves the immune privilege of the eye. It was reported that a mild, chronic IOP elevation was induced for at least 15 weeks following an initial IOP spike that appeared immediately after suture placement.…”

mentioning

confidence: 99%

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

Liu

Flanagan

2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To develop a chronic ocular hypertension mouse model by inducing intraocular pressure (IOP) elevation using a suture technique previously developed for rats.METHODS. C57BL/6 mice were given monocular circumlimbal suture (10/0) placement under anesthesia (ketamine/xylazine). The suture was left in place for 12 weeks (n ¼ 10). A control group had the same treatment while it was removed after day 1 (n ¼ 10). Intraocular pressure, electroretinogram (ERG), and optical coherence tomography (OCT) were measured in both groups for 12 weeks. At week 12, animals were euthanized and retina was harvested for histologic assessment.RESULTS. In the group with extended suture placement, IOP spiked from 14.3 6 0.9 to 48.4 6 4.8 mm Hg immediately after suture implantation. At day 1, it declined to 33.2 6 3.7 mm Hg and remained elevated for 12 weeks. In the suture removal group, IOP normalized to baseline within a day following suture removal. In the group with prolonged IOP elevation, the retinal ganglion cell (RGC) mediated ERG responses continued to exacerbate and were significantly reduced by week 12 (P < 0.001). Progressive loss of retinal nerve fiber layer was found and it became significant from week 4 (P < 0.001). At week 12, significant loss of RGCs (P < 0.001) was noted. In the IOP normalization group, no alteration in ERG, OCT, and RGC counting was observed.CONCLUSIONS. The circumlimbal suture approach produces a mild chronic IOP elevation in mice. Functional and structural changes under model induction are largely independent of the initial IOP spike.Keywords: glaucoma, intraocular pressure, electroretinogram, optical coherence tomography, ganglion cell G laucoma is a chronic ocular disease, which is characterized by selective retinal ganglion cell (RGC) degeneration and progressive visual field loss. Elevated intraocular pressure (IOP) is a critical risk factor for disease development, and IOP lowering is the mainstay of disease management. [1][2][3] Over the past few decades, a variety of rodent models have been developed to simulate human glaucoma. [4][5][6][7] These models aim to induce either acute or chronic ocular hypertension leading to glaucomatous-like changes. By using such models, investigators have made significant insights into understanding the pathogenesis of the disease.Previously, a rat model of chronic IOP elevation using conjunctival circumlimbal suture was developed. 8,9 This minimally invasive technique employed the concept of oculopression to produce elevated IOP. [10][11][12] An advantage of the suture compression model is that it is not associated with ocular tissue penetration or traumatization, and therefore relatively preserves the immune privilege of the eye. It was reported that a mild, chronic IOP elevation was induced for at least 15 weeks following an initial IOP spike that appeared immediately after suture placement. Progressive loss of RGC function, retinal nerve fiber layer (RNFL) defect, and eventual cell death in the ganglion cell layer were observed under model induction, ...

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Dynamics, Alterations, and Consequences of Minimally Invasive Intraocular Pressure Elevation in Rats

Cited by 16 publications

References 35 publications

Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model

Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model

In vivo imaging methods to assess glaucomatous optic neuropathy

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

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