Review of rodent hypertensive glaucoma models

Abstract

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.

Changes of Ocular Dimensions as a Marker of Disease Progression in a Murine Model of Pigmentary Glaucoma

“…The preclinical assessment of drugs aimed at lowering IOP has been traditionally performed on monkeys with artificially increased IOP (Wang et al, 2000), but such experiments are prohibitively expensive and currently rarely conducted due to ethical reasons. Instead, following the development of non-invasive technologies of IOP measurement applicable to small animals, IOP-dependent rodent models have become popular, in which OH is artificially induced (Millar and Pang, 2015;Biswas and Wan, 2019). Although these models reproduce certain aspects of human glaucoma, since retinal ganglion cell (RGC) loss does not develop naturally, an increase in IOP is usually abrupt and may not be long-lasting, and inflammatory components due to physical injury may be a confounding factor.…”

Extended Ganglion Cell Layer Thickness Deviation Maps With OCT in Glaucoma Diagnosis

“…Glaucoma is a multifactorial disease with an elevated IOP as most important risk factor, known until now (19). Several studies showed that an increased IOP leads to RGC loss (20)(21)(22)(23)(24)(25). One molecular mechanism might be seen in the presence of mechanosensitive Piezo channels within the GCL (26).…”

“…As an increased IOP induced RGC loss (20)(21)(22)(23)(24)(25), devices, investigating thickness of single RGC layer, might improve the diagnostic value of GCC/GCIPL. SPECTRALIS R offers the possibility of analysis of single GCL layer in a defined macular region with different grids.…”

A subacute model of glaucoma based on limbal plexus cautery in pigmented rats

“…Widely used experimental models of glaucoma have been classified as pre-trabecular, trabecular or post-trabecular, using the trabecular meshwork (TM) as an anatomic reference 17 . Multiple limitations have, however, been reported: (1) intracameral injection of viscoelastic substances or microbead particles (pre-trabecular) 18,19 is invasive, with high risk of corneal damage or inflammation, as well as intraocular infections; moreover, some injected substances may reduce the transparency of the optic media, which precludes functional analysis; (2) laser scarring of the TM and/or photocoagulation of the limbal vasculature and episcleral veins (trabecular) 20,21 require expensive equipment, are difficult to apply to pigmented animals due to high and variable absorption of laser energy, and is often accompanied by damage to the TM, corneal inflammation and ulceration, which impair functional assessment 22 ; (3) Morrison’s procedure of injection of hypertonic saline into an episcleral vein (post-trabecular) 23 requires extensive training, and leads to highly variable IOP 7,24 ; (4) Shareef and Sharma’s episcleral vein cauterization (EVC) 25 is also invasive, requires a slow learning curve to access the deep episcleral veins behind the rectus muscles, may lead to venous congestion because the targeted deep venous plexus actually comprises the vortex veins, which drain the entire globe including the choroid 26,27 , and leads to highly variable period of OHT, ranging from 2 weeks to 6–7 months as described by differing authors 25,28,29 .…”