Animal models of glucocorticoid-induced glaucoma

Abstract

Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG.

Dexamethasone-Induced Ocular Hypertension in Mice

“…Animal models can provide better insights into pathogenesis of GC-induced OHT, and investigators have reported GC-OHT in eight different species besides human. 4 In our study, we describe a mouse model of GC-OHT with a novel periocular CF delivery of DEX-Ac. This reproducible model is easy to run and captures many aspects of GC-induced OHT, including elevated IOP, reduction in the aqueous humor outflow facility, and reversibility of ocular hypertension after discontinuing GC treatment.…”

“…4 The routes of GC administration in treatment of these disorders can be topical ocular, oral, systemic, intravitreal injections and implants, and periocular injections (including subconjunctival, subtenon, retrobulbar, and peribulbar).…”

“…2,3 GCs also remain the mainstay of treatment for a variety of ocular inflammatory diseases involving almost all tissues of the eye, such as eyelids, conjunctiva, cornea, sclera, uvea, retina, and optic nerve. 4 The routes of GC administration in treatment of these disorders can be topical ocular, oral, systemic, intravitreal injections and implants, and periocular injections (including subconjunctival, subtenon, retrobulbar, and peribulbar). 5 However, prolonged GC therapy is associated with serious ocular adverse effects, including development of posterior subcapsular cataracts, and the development of GC-induced ocular hypertension (GC-OHT) and iatrogenic open-angle glaucoma.…”

Severe Corticosteroid-Induced Ocular Hypertension Requiring Bilateral Trabeculectomies in a Patient with Takayasu’s Arteritis

“…Although the exact pathophysiology is not fully understood, glucocorticoids appear to act directly on trabecular meshwork (TM) cells to influence cellular, biochemical, and molecular changes that ultimately lead to reduced outflow facility [3, 4]. Glucocorticoids alter the organization of the actin cytoskeleton and induce the formation of so-called cross-linked actin networks (CLANs) in TM, leading to increased outflow resistance [5].…”

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model

“…While the nonhuman primate experimental glaucoma model (Burgoyne, 2015b) benefits from optic nerve head (ONH) anatomy and physiology that is similar to the human ONH, the model is impractical for studies that require large sample sizes. By contrast, rodent models (Crowston et al, 2015; Fernandes et al, 2015; Morgan and Tribble, 2015; Morrison et al, 2015; Overby and Clark, 2015; Pang et al, 2015) display pathophysiologic changes that are comparable to human glaucoma, despite substantial differences in ONH anatomy.…”