Methods to Induce Chronic Ocular Hypertension

Abstract

Glaucoma, a form of progressive optic neuropathy, is the second leading cause of blindness worldwide. Being a prominent disease affecting vision, substantial efforts are being made to better understand glaucoma pathogenesis and to develop novel treatment options including neuroprotective and neuroregenerative approaches. Cell transplantation has the potential to play a neuroprotective and/or neuroregenerative role for various ocular cell types (e.g., retinal cells, trabecular meshwork). Notably, glaucoma is often associated with elevated intraocular pressure, and over the past 2 decades, several rodent models of chronic ocular hypertension (COH) have been developed that reflect these changes in pressure. However, the underlying pathophysiology of glaucoma in these models and how they compare to the human condition remains unclear. This limitation is the primary barrier for using rodent models to develop novel therapies to manage glaucoma and glaucoma-related blindness. Here, we review the current techniques used to induce COH-related glaucoma in various rodent models, focusing on the strengths and weaknesses of the each, in order to provide a more complete understanding of how these models can be best utilized. To so do, we have separated them based on the target tissue (pre-trabecular, trabecular, and post-trabecular) in order to provide the reader with an encompassing reference describing the most appropriate rodent COH models for their research. We begin with an initial overview of the current use of these models in the evaluation of cell transplantation therapies.

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

“…In this work we analyzed two different Ms sizes (small: 20/10; and large: 38/20) and compared them with the well-established Morrison model (EPI) [ 28 ]. Although in many previous studies researchers injected beads into the anterior chamber, they all used non-biodegradable materials [ 5 ]. This is the case of [ 8 ] the glaucomatous effect comparison after injecting a suspension (2 microliters) of non-biodegradable polystyrene microparticles of different sizes and concentrations: 10 microns (106 beads/mL) and 15 microns (5 × 106 beads/mL) into the anterior chamber.…”

“…In order to broaden and improve knowledge of glaucomatous pathologies, several animal models have been developed in recent decades applying a significant increase in IOP secondary to a decrease in outflow of aqueous humor. To this, either laser, cauterization, ligature and/or episcleral vein sclerosis or mechanical blockage of the trabecular meshwork with obstructive substances (hyaluronic acid or paramagnetic, latex or polystyrene beads injected into the anterior chamber) have been used [ 5 ]. All these models produce a sudden, short increase in IOP resulting in limited RGC and axonal damage.…”

Hypotensive Effect of Nanomicellar Formulation of Melatonin and Agomelatine in a Rat Model: Significance for Glaucoma Therapy

“…The model of increased IOP was obtained by injecting the anterior chamber of the rat eye with methylcellulose, a molecule that leads to ocular hypertension by mechanically blocking the outflow of the aqueous humor [23]. The injection of viscoelastic substances causes a viscosity-dependent ocular hypertension by blocking the trabecular meshwork channel, thus rendering the methylcellulose model similar to the microbead injection models [24]. Rats were anesthetized with an intraperitoneal injection of pentobarbital (30 mg/kg) and injected in both eyes with 15 µL of 2% methylcellulose in sterile saline through an 18G needle under a microscope.…”

A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma

“…Although the eye anatomy in rodents differs from that in humans, the similarity in the conventional outflow pathway renders the rodent eye a suitable model to mimic the changes observed in human glaucomatous eyes. In rodent models, IOP elevation can be obtained by increasing aqueous humor outflow resistance as for instance through the blockade of the trabecular meshwork or through the closure of episcleral veins [22].…”

“…This model was developed in rabbits [23] and successfully applied in the rats [24]. In the present study, the MCE model was established in mice taking into consideration that the anatomy and the physiology of the aqueous humor outflow does not differ between rats and mice [22]. In addition, in mice, hydroxypropyl MCE is able to increase the microbeads-induced IOP elevation due to the high viscosity of MCE and its derivatives [25].…”