The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and Mice

Sappington, Rebecca M.; Carlson, Brian J.; Crish, Samuel D.; Calkins, David J.

doi:10.1167/iovs.09-3947

Cited by 339 publications

(364 citation statements)

References 25 publications

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“…This suggests that, although IOP cannot predict a deficit, aging can influence the likelihood of one for a given IOP. We tested this directly by comparing CTB in the SC of young (3-4 mo) and moderately aged (7-9 mo) rats with equivalent IOP elevations induced acutely (27). For both groups, injection of polystyrene microbeads into the aqueous chamber of the eye induced a 45% elevation in IOP compared with an equal volume of saline solution (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DBA/2 and C57BL/6 mice were obtained from Jackson Laboratories and Brown Norway rats from Charles River. Animals were maintained in a 12-h light/dark cycle with standard rodent chow available ad libitum as described (27,30). For acute elevation of IOP, we used microbead occlusion of aqueous flow as described (27).…”

Section: Methodsmentioning

confidence: 99%

“…Animals were maintained in a 12-h light/dark cycle with standard rodent chow available ad libitum as described (27,30). For acute elevation of IOP, we used microbead occlusion of aqueous flow as described (27). IOP was measured in a subset of DBA/2 mice and in awake rats using the Tono-Pen XL (Medtronic Solan) as described previously (27,30).…”

Section: Methodsmentioning

confidence: 99%

“…For acute elevation of IOP, we used microbead occlusion of aqueous flow as described (27). IOP was measured in a subset of DBA/2 mice and in awake rats using the Tono-Pen XL (Medtronic Solan) as described previously (27,30).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Crish

Sappington

Inman

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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316

482

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An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.axon transport | optic neuropathy | retinal ganglion cell | glaucoma | optic nerve

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Crish

Sappington

Inman

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

316

482

View full text Add to dashboard Cite

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“…Recently, we and others developed a convenient method of reproducibly inducing chronic IOP elevation in mice by anterior chamber injection of polystyrene microbeads. 37,38 With this mouse model, we investigated the functions of NGB in the retina and, using mouse genetic tools, demonstrated a role of NGB in promoting RGC survival by reducing oxidative stress and improving mitochondrial function in glaucoma. These findings offer a unique opportunity for neuroprotective interventions aimed at effective control of neuronal damage in glaucoma.…”

mentioning

confidence: 99%

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Wei

Cho

et al. 2011

The American Journal of Pathology

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Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Neuroglobin (NGB) is a novel member of the globin superfamily that is distantly related to hemoglobin and myoglobin. 1 A highly conserved protein in evolution, human and mouse Ngb, both comprised of 151 amino acids, are 94% identical. 2,3 In mammals, expression of NGB is found in the brain, retina, and other nerve tissues, predominantly in neurons but absent from glial cells. 4 -7 Distribution of NGB protein in the normal human retina is very similar to what has been described in mice: NGB is detected primarily in the plexiform layers and photoreceptor inner segments, which are rich in mitochondria and synapses and consume high amounts of oxygen. 8,9 NGB has been shown to act as an endogenous neuroprotective molecule that enhances neuronal survival under hypoxic-ischemic insults in the brain 10 -12 ; however, its physiological functions and molecular mode of actions are not fully understood. Of note, NGB is present at a 100-fold greater concentration in the retina than in the brain, 8,[13][14][15] suggesting that the retina may be its most important site of function; however, among the many unknown roles of NGB, functional significance of NGB expression in the retina has been largely unexplored.

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Localized and Controlled Delivery of Nitric Oxide to the Conventional Outflow Pathway via Enzyme Biocatalysis: Toward Therapy for Glaucoma

et al. 2017

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Nitric oxide (NO) is able to lower intraocular pressure (IOP); however, its therapeutic effects on outflow physiology are location‐ and dose‐dependent. A NO delivery platform that directly targets the resistance‐generating region of the conventional outflow pathway and locally liberates a controlled dose of NO is reported. An increase in outflow facility (decrease in IOP) is demonstrated in a mouse model.

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The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and Mice

Abstract: These data support a novel and flexible model of modest ocular hypertension with axon loss. The maximal duration of IOP elevation will be further characterized in future studies.

Cited by 339 publications

References 25 publications

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Localized and Controlled Delivery of Nitric Oxide to the Conventional Outflow Pathway via Enzyme Biocatalysis: Toward Therapy for Glaucoma

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