A rat experimental model of glaucoma incorporating rapid-onset elevation of intraocular pressure

Smędowski, Adrian; Pietrucha‐Dutczak, Marita; Kaarniranta, Kai; Lewin–Kowalik, Joanna

doi:10.1038/srep05910

Cited by 49 publications

(45 citation statements)

References 43 publications

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“…Moreover, reliable animal models are needed to assess the therapeutic value of drugs in preclinical trials (Smedowski et al, 2014). However, since differences in retinal anatomy and physiology between animal species exist, and the procedures used to obtain such experimental models may vary, it is necessary to ascertain the advantages and limitations of a particular model, and carefully choose the pertinent one in function of the damage caused to the optic nerve and the reproducibility (Smedowski et al, 2014;Vecino, 2008).…”

Section: Glaucomamentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

638

533

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The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

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Section: Glaucomamentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

638

533

View full text Add to dashboard Cite

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“…Most of this work has been done in mice and they show only a low to moderate level of damage in the optic nerve with wide variation in the results and inconsistent data [43][44][45][46][47][48][49][50] . When using rats, the duration of elevated IOP was too short to cause enough damage to cells 48 .…”

Section: Representative Resultsmentioning

confidence: 99%

“…Even with modifications to the procedure, the model still caused severe damage in short duration representing an acute neuropathic model rather than a chronic glaucoma model 51 . Smedowski et al 43 have recently developed a further modified microbead procedure using an additional initial 'high pressure injury' to achieve longer lasting IOP elevation with chronic damage that does show promise. More studies using this technique are necessary to further validate this model.…”

Section: Representative Resultsmentioning

confidence: 99%

Glaucoma-inducing Procedure in an <em>In Vivo </em>Rat Model and Whole-mount Retina Preparation

Gossman

Linn

2016

JoVE

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Glaucoma is a disease of the central nervous system affecting retinal ganglion cells (RGCs). RGC axons making up the optic nerve carry visual input to the brain for visual perception. Damage to RGCs and their axons leads to vision loss and/or blindness. Although the specific cause of glaucoma is unknown, the primary risk factor for the disease is an elevated intraocular pressure. Glaucoma-inducing procedures in animal models are a valuable tool to researchers studying the mechanism of RGC death. Such information can lead to the development of effective neuroprotective treatments that could aid in the prevention of vision loss. The protocol in this paper describes a method of inducing glaucomalike conditions in an in vivo rat model where 50 µl of 2 M hypertonic saline is injected into the episcleral venous plexus. Blanching of the vessels indicates successful injection. This procedure causes loss of RGCs to simulate glaucoma. One month following injection, animals are sacrificed and eyes are removed. Next, the cornea, lens, and vitreous are removed to make an eyecup. The retina is then peeled from the back of the eye and pinned onto sylgard dishes using cactus needles. At this point, neurons in the retina can be stained for analysis. Results from this lab show that approximately 25% of RGCs are lost within one month of the procedure when compared to internal controls. This procedure allows for quantitative analysis of retinal ganglion cell death in an in vivo rat glaucoma model. Video LinkThe video component of this article can be found at

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“…An initial high‐pressure injury equating to a severe glaucoma attack was proposed to improve the distribution of beads in the AC and the triggering of the pressure‐related cellular death cascades (Smedowski et al. ). This model achieved longer lasting IOP elevation resulting in RGC damage without the need of retreatment.…”

Section: Hypertensive Glaucoma Modelsmentioning

confidence: 99%

Review of rodent hypertensive glaucoma models

Biswas

Wan

2018

Acta Ophthalmologica

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Glaucoma is a neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is a primary risk factor for the development and progression of glaucoma. Rodent models of glaucoma have greatly improved our understanding of the pathophysiology of glaucoma and served as a useful tool to investigate neuroprotective agents. An ideal glaucoma animal model should be easy to induce, reproducible, biologically plausible and predictable. Of the available animal models of glaucoma, rodents are commonly studied because they have a relatively short life span and can be genetically altered. A successful hypertensive glaucoma model should induce structural glaucomatous changes: including loss of retinal nerve fibres, retinal ganglion cells and optic-disc cupping along with IOP elevation. The level and duration of IOP elevation should be titratable depending on the targeted glaucomatous damage. This review summarizes the outcomes of induced rodent hypertensive glaucoma models including intracameral injection of microbeads, laser photocoagulation, episcleral vein cauterization, injection of hypertonic saline and hyaluronic acid. We aim to provide a detailed overview of each of the models with a focus on parameters that defines a successful glaucoma model. The induced IOP elevation and duration of elevation varied among the different models and strain of rodent; nonetheless, they all achieved a sustainable raised IOP with corresponding RGC loss. The limitations of each model are discussed.

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A rat experimental model of glaucoma incorporating rapid-onset elevation of intraocular pressure

Cited by 49 publications

References 43 publications

Glia–neuron interactions in the mammalian retina

Glia–neuron interactions in the mammalian retina

Glaucoma-inducing Procedure in an <em>In Vivo </em>Rat Model and Whole-mount Retina Preparation

Review of rodent hypertensive glaucoma models

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