Microbead models in glaucoma

Morgan, James I.; Tribble, James R.

doi:10.1016/j.exer.2015.06.020

Cited by 65 publications

(47 citation statements)

References 27 publications

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“…However, neither a quantitative description of glaucomatous structural change nor a strategy for its staging (independent of the magnitude of RGC axon loss) 6 currently exists. Building the tools for characterizing the phenotype of a glaucomatous optic neuropathy is necessary for human patient care 1,15 (i.e., the detection of structural glaucoma) and also necessary for the development of animal models of glaucoma that occur at normal 26,32,33 and elevated levels 6,14,34,35 of IOP.…”

Section: Discussionmentioning

confidence: 99%

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

Ing

Ivers

Yang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeTo use optical coherence tomography (OCT) to test the hypothesis that optic nerve head (ONH) “cupping” in the monkey optic nerve transection (ONT) model does not include posterior laminar deformation.MethodsFive monkeys (aged 5.5–7.8 years) underwent ONH and retinal nerve fiber layer (RNFL) OCT imaging five times at baseline and biweekly following unilateral ONT until euthanization at ∼40% RNFL loss. Retinal nerve fiber layer thickness (RNFLT) and minimum rim width (MRW) were calculated from each pre- and post-ONT imaging session. The anterior lamina cribrosa surface (ALCS) was delineated within baseline and pre-euthanasia data sets. Significant ONT versus control eye pre-euthanasia change in prelaminar tissue thickness (PLTT), MRW, RNFLT, and ALCS depth (ALCSD) was determined using a linear mixed-effects model. Eye-specific change in each parameter exceeded the 95% confidence interval constructed from baseline measurements.ResultsAnimals were euthanized 49 to 51 days post ONT. Overall ONT eye change from baseline was significant for MRW (−26.2%, P = 0.0011), RNFLT (−43.8%, P < 0.0001), PLTT (−23.8%, P = 0.0013), and ALCSD (−20.8%, P = 0.033). All five ONT eyes demonstrated significant eye-specific decreases in MRW (−23.7% to −31.8%) and RNFLT (−39.6% to −49.7%). Four ONT eyes showed significant PLTT thinning (−23.0% to −28.2%). The ALCS was anteriorly displaced in three of the ONT eyes (−25.7% to −39.2%). No ONT eye demonstrated posterior laminar displacement.ConclusionsSeven weeks following surgical ONT in the monkey eye, ONH cupping involves prelaminar and rim tissue thinning without posterior deformation of the lamina cribrosa.

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Section: Discussionmentioning

confidence: 99%

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

Ing

Ivers

Yang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…To address these issues and explore any neuroinflammation throughout the visual pathway in glaucoma, we fully characterise inflammatory changes in an inducible rat model of ocular hypertensive glaucoma in which intraocular pressure is elevated by intracameral (anterior chamber) injection of paramagnetic beads to occlude the drainage structures of the eye (23,24). This results in sustained ocular hypertension driving a reproducible and significant loss of retinal ganglion cell numbers as well as neuroinflammation (without uveitis).…”

Section: Introductionmentioning

confidence: 99%

When is a control not a control? Reactive microglia occur throughout the control contralateral visual pathway in experimental glaucoma

Tribble

Kokkali

Otmani

et al. 2019

Preprint

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Background: Glaucoma remains a leading cause of irreversible blindness worldwide. Multiple animal models show retinal ganglion cell injuries that replicate features of glaucoma. In these experiments the contralateral eye is commonly used as an internal control. As in humans, in rodents and non-human primates there is significant cross-over of retinal ganglion cell axons from the ipsilateral to the contralateral side at the level of the optic chiasm which may confound findings when damage is restricted to one eye. While neuroinflammation may be a critical event that damages retinal ganglion cells and their axons during glaucoma progression the effect of unilateral damage on the contralateral visual pathway has largely been unexplored.Methods: Ocular hypertensive glaucoma was induced unilaterally or bilaterally by intracameral injection of paramagnetic beads in adult Brown Norway rats. Retinal ganglion cell neurodegeneration and dysfunction were assessed. Neuroinflammation was quantified in the retina, optic nerve head, optic nerve, lateral geniculate nucleus, and superior colliculus by high resolution imaging, and in the retina by flow cytometry and protein arrays.Results: Following ocular hypertensive stress the retinal vasculature remodels, peripheral monocytes enter the retina, and microglia become highly reactive. This effect is more marked in animals with bilateral induction of ocular hypertensive glaucoma. In rats where glaucoma was induced unilaterally there was significant microglia activation in the contralateral (control) eye. Microglial activation extended into the optic nerve and terminal visual thalami, where it was similar across hemispheres irrespective of whether ocular hypertension was unilateral or bilateral. Conclusions:Ocular hypertensive glaucoma in the rat recapitulates many of the features of human glaucoma. In this model microglia become reactive throughout the visual pathway during glaucoma pathogenesis. These effects are not isolated to the experimental eye and its pathway and significant neuroinflammation occurs in the contralateral 'control' eye and pathway. These data suggest that caution is warranted when using the contralateral eye as control in unilateral models of glaucomatous damage.

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“…A variety of rodent ocular hypertension models are available for modeling glaucoma (for reviews see [161,162]). Methods to raise intraocular pressure include restricting aqueous outflow by damaging venous drainage from the anterior chamber or by blocking the access of aqueous humor to the trabecular meshwork with microbeads.…”

Section: 0 Bdnf/trkb In Glaucomamentioning

confidence: 99%

Role of BDNF/TrkB pathway in the visual system: therapeutic implications for glaucoma

Mysona

Zhao

Bollinger

2016

Expert Review of Ophthalmology

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Summary Introduction Neuroprotective therapeutics are needed to treat glaucoma, an optic neuropathy that results in death of retinal ganglion cells (RGCs). Areas covered The BDNF/TrkB pathway is important for RGC survival. Temporal and spatial alterations in the BDNF/TrkB pathway occur in development and in response to acute optic nerve injury and to glaucoma. In animal models, BDNF supplementation is successful at slowing RGC death after acute optic nerve injury and in glaucoma, however, the BDNF/TrkB signaling is not the only pathway supporting long term RGC survival. Expert Commentary Much remains to be discovered about the interaction between retrograde, anterograde, and retinal BDNF/TrkB signaling pathways in both neurons and glia. An ideal therapeutic agent for glaucoma likely has several modes of action that target multiple mechanisms of neurodegeneration including the BDNF/TrkB pathway.

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Microbead models in glaucoma

Cited by 65 publications

References 27 publications

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

When is a control not a control? Reactive microglia occur throughout the control contralateral visual pathway in experimental glaucoma

Role of BDNF/TrkB pathway in the visual system: therapeutic implications for glaucoma

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