A Novel Tree Shrew (Tupaia belangeri) Model of Glaucoma

Abstract

PurposePrimates and rodents are used widely as animal models of glaucoma, but each has significant limitations. Researchers need additional animal models that closely resemble the relevant anatomy and pathologic features of the human disease to more quickly advance research. We validate a novel glaucoma animal model in tree shrews (Tupaia belangeri).MethodsExperimental glaucoma was induced in adult tree shrews (n = 8) by injecting 50 μL of a 25 mg/mL ferromagnetic bead solution into the anterior chamber. Beads were directed into the iridocorneal angle with a magnet to impede aqueous outflow. Animals were followed for 3 months with weekly IOP measurements and biweekly spectral domain optical coherence tomography (SD-OCT) images of the optic nerve head. Histopathology of the optic nerve and optic nerve axon counts were completed at the end of the study.ResultsThe 12-week average mean IOP was 22.7 ± 3.6 and 8.6 ± 2.9 mm Hg in the treated and control eyes, respectively. Longitudinal analysis showed significant retinal nerve fiber layer (RNFL) thinning throughout the study. Axon counts were significantly reduced (59.7%) in treated versus control eyes. SD-OCT imaging showed cupping and posterior displacement of the lamina cribrosa in glaucomatous eyes. RNFL thickness and optic nerve axon counts were reduced consistent with IOP elevation. Optic nerves demonstrated histopathology consistent with glaucomatous optic neuropathy.ConclusionsTree shrews with experimental glaucoma show key pathologic characteristics of the human disease. The tree shrew model of glaucoma has the potential to help researchers accelerate our understanding of glaucoma pathophysiology.

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

“…Retinal ganglion cell degeneration is described as a compartmentalised process, where the soma, axon, and dendritic atrophy and loss differs temporally based on the insult context (49)(50)(51). Retinal ganglion cell soma and axon loss is a feature of human glaucoma that is replicated across different animal models in multiple species (50,(52)(53)(54)(55). Dendritic atrophy in the inner plexiform layer is also well established, and can be substantial even with mild retinal ganglion cell loss (56)(57)(58).…”

Retino-Cortical Mapping Ratio Predicts Columnar and Salt-and-Pepper Organization in Mammalian Visual Cortex

“…The anatomical data used in this study were from Adams et al (2007), Van Hooser et al (2005, Kong et al (2010), Nauhaus et al (2016), Ross and Kay (2004), Nauhaus et al (2012) for macaque; from Van Hooser et al 2005, Hughes (1975), Ohki et al (2005), Ross and Kay (2004), Tusa et al (1978), Ohki et al, (2006) for cat; from Henderson (1985), Henderson et al (1988), Van Hooser et al (2005, Hupfeld et al (2006), Law et al (1988), Li et al (2008), Sun et al (2016) for ferret; from Engelmann andPeichl (1996), Van Hooser et al (2005), Johnson et al (2010), Keil et al (2012), Samuels et al (2018), Sesma et al (1984) for tree shrew; from Howland et al 2004, Hughes (1971), Oyster et al (1981), Pak (1984), Ross and Kay (2004) for rabbit; from Van Hooser et al 2005, Johnson et al (1998), Ross and Kay (2004) for gray squirrel; from Espinoza andThomas (1983), Van Hooser et al (2005), Hughes (1979), Ohki et al (2005), Ross and Kay (2004), Ch'ng and Reid 2010 Table 1.…”

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia

“…Probably, this discrepancy was due to the disease models with different species of animals and different experimental strategies for ischemia or hypoxia conditioning. We chose tree shrews largely because they closely resemble human ocular anatomy and pathologic features of the human retinal diseases [27]. For example, the retina from a tree shrew is dominated by cone cells and tree shrews have good color vision and high color discrimination accuracy and are sensitive to light and darkness [28][29][30].…”